Skip to content
2000
image of Exploring the Interplay of PI3K/AKT/mTOR and JNK Signaling Pathways in Psoriasis: Insights from Systematic Review and Network Pharmacology Approach

Abstract

Introduction

Psoriasis is a chronic inflammatory skin disease characterized by excessive keratinocyte proliferation, abnormal differentiation, and infiltration of inflammatory cells. Central to its pathogenesis are the PI3K/AKT/mTOR and JNK signaling pathways, which regulate inflammation and keratinocyte behavior.

Methods

This study reviewed experimental data reported in the scientific literature and utilized network pharmacology to investigate the interplay between the PI3K/AKT/mTOR and JNK pathways, aiming to elucidate the underlying mechanisms of psoriasis. 709 records from Scopus, Web of Sciences, Cochrane Library and PubMed were reviewed without limitations until October 3, 2023. 85 articles were included in the systematic review.

Results

Key molecules, including EGFR, Sortilin, and Cyr61, were identified as important links between these pathways, influencing cell survival and apoptosis. Flavonoids such as Rhododendrin, Erianin, and Fisetin were found to effectively target both of these pathways, potentially modifying cellular behavior and offering therapeutic benefits. The network analysis revealed that EGFR and AKT serve as critical connectors between hub genes CDC42 and GAPDH, with these flavonoids impacting downstream signaling molecules, including PI3K, AKT, mTOR, Grb2, JAK, STAT, Cyclooxygenase, HIF-1α, and MAPKs.

Discussion

The findings highlight the pivotal role of the PI3K/AKT/mTOR pathway in promoting inflammation and cellular proliferation by activating NF-κB and HIF-1α.

Conclusion

This comprehensive review underscores the importance of the PI3K/AKT/mTOR and JNK pathways in understanding psoriasis mechanisms. Targeting these pathways with flavonoids may offer promising therapeutic strategies by modulating key molecular hubs involved in disease progression.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpb/10.2174/0113892010380506250909114143
2025-10-02
2025-12-14

  • From This Site

    /content/journals/cpb/10.2174/0113892010380506250909114143
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Greb J.E. Goldminz A.M. Elder J.T. Lebwohl M.G. Gladman D.D. Wu J.J. Mehta N.N. Finlay A.Y. Gottlieb A.B. Psoriasis. Nat. Rev. Dis. Primers 2016 2 1 16082 10.1038/nrdp.2016.82 27883001
    [Google Scholar]
  2. Haneke E. Nail psoriasis: Clinical features, pathogenesis, differential diagnoses, and management. Psoriasis 2017 7 51 63 10.2147/PTT.S126281 29387608
    [Google Scholar]
  3. Ebrahimi A. Mehrabi M. Miraghaee S.S. Mohammadi P. Fatehi Kafash F. Delfani M. Khodarahmi R. Flavonoid compounds and their synergistic effects: Promising approaches for the prevention and treatment of psoriasis with emphasis on keratinocytes – A systematic and mechanistic review. Int. Immunopharmacol. 2024 138 112561 10.1016/j.intimp.2024.112561 38941673
    [Google Scholar]
  4. Damiani G. Bragazzi N.L. Karimkhani Aksut C. Wu D. Alicandro G. McGonagle D. Guo C. Dellavalle R. Grada A. Wong P. La Vecchia C. Tam L.S. Cooper K.D. Naghavi M. The global, regional, and national burden of psoriasis: Results and insights from the global burden of disease 2019 study. Front. Med. 2021 8 743180 10.3389/fmed.2021.743180 34977058
    [Google Scholar]
  5. Gonzalez J. Cunningham K. Perlmutter J. Gottlieb A. Systematic review of health-related quality of life in adolescents with psoriasis. Dermatology 2016 232 5 541 549 10.1159/000450826 27811471
    [Google Scholar]
  6. Strober B. Karki C. Mason M. Guo N. Holmgren S.H. Greenberg J.D. Lebwohl M. Characterization of disease burden, comorbidities, and treatment use in a large, US-based cohort: Results from the Corrona Psoriasis Registry. J. Am. Acad. Dermatol. 2018 78 2 323 332 10.1016/j.jaad.2017.10.012 29051036
    [Google Scholar]
  7. Dubois Declercq S. Pouliot R. Promising new treatments for psoriasis. ScientificWorldJournal 2013 2013 1 980419 10.1155/2013/980419 23935446
    [Google Scholar]
  8. Lebwohl M. Ali S. Treatment of psoriasis. Part 1. Topical therapy and phototherapy. J. Am. Acad. Dermatol. 2001 45 4 487 502 10.1067/mjd.2001.117046 11568737
    [Google Scholar]
  9. Armstrong AW 2023
  10. Zhang P. Wu M.X. A clinical review of phototherapy for psoriasis. Lasers Med. Sci. 2018 33 1 173 180 10.1007/s10103‑017‑2360‑1 29067616
    [Google Scholar]
  11. Kelly J.B. Foley P. Strober B.E. Current and future oral systemic therapies for psoriasis. Dermatol. Clin. 2015 33 1 91 109 10.1016/j.det.2014.09.008 25412786
    [Google Scholar]
  12. Lozano R. Fullman N. Abate D. Abay S.M. Abbafati C. Abbasi N. Abbastabar H. Abd-Allah F. Zamani M. Zare Z. Zavala-Arciniega L. Zegeye D.T. Zegeye E.A. Zeleke A.J. Zendehdel K. Zerfu T.A. Zhang A.L. Zhang X. Zhou M. Zhu J. Zimsen S.R.M. Zodpey S. Zoeckler L. Zucker I. Zuhlke L.J.J. Lim S.S. Murray C.J.L. Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related sustainable development goals for 195 countries and territories: A systematic analysis for the global burden of disease study 2017. Lancet 2018 392 10159 2091 2138 10.1016/S0140‑6736(18)32281‑5 30496107
    [Google Scholar]
  13. Kamata M. Tada Y. Crosstalk: Keratinocytes and immune cells in psoriasis. Front. Immunol. 2023 14 1286344 10.3389/fimmu.2023.1286344 38022549
    [Google Scholar]
  14. Sieminska I. Pieniawska M. Grzywa T.M. The immunology of psoriasis—Current concepts in pathogenesis. Clin. Rev. Allergy Immunol. 2024 66 2 164 191 10.1007/s12016‑024‑08991‑7 38642273
    [Google Scholar]
  15. Zhou X. Chen Y. Cui L. Shi Y. Guo C. Advances in the pathogenesis of psoriasis: From keratinocyte perspective. Cell Death Dis. 2022 13 1 81 10.1038/s41419‑022‑04523‑3 35075118
    [Google Scholar]
  16. Zeke A. Misheva M. Reményi A. Bogoyevitch M.A. JNK signaling: Regulation and functions based on complex protein-protein partnerships. Microbiol. Mol. Biol. Rev. 2016 80 3 793 835 10.1128/MMBR.00043‑14 27466283
    [Google Scholar]
  17. Bode A.M. Dong Z. The functional contrariety of JNK. Mol. Carcinog. 2007 46 8 591 598 10.1002/mc.20348 17538955
    [Google Scholar]
  18. Davis R.J. Signal transduction by the JNK group of MAP kinases. Cell 2000 103 2 239 252 10.1016/S0092‑8674(00)00116‑1 11057897
    [Google Scholar]
  19. Weston C.R. Davis R.J. The JNK signal transduction pathway. Curr. Opin. Cell Biol. 2007 19 2 142 149 10.1016/j.ceb.2007.02.001 17303404
    [Google Scholar]
  20. Buerger C. Shirsath N. Lang V. Berard A. Diehl S. Kaufmann R. Boehncke W.H. Wolf P. Inflammation dependent mTORC1 signaling interferes with the switch from keratinocyte proliferation to differentiation. PLoS One 2017 12 7 e0180853 10.1371/journal.pone.0180853 28700632
    [Google Scholar]
  21. Balato A. Lembo S. Ayala F. Balato N. Caiazzo G. Raimondo A. Di Caprio R. Monfrecola G. Mechanistic target of rapamycin complex 1 is involved in psoriasis and regulated by anti‐TNF‐α treatment. Exp. Dermatol. 2017 26 4 325 327 10.1111/exd.13267 27943462
    [Google Scholar]
  22. Shirsath N. Mayer G. Singh T.P. Wolf P. 8‐methoxypsoralen plus UVA (PUVA) therapy normalizes signalling of phosphorylated component of mTOR pathway in psoriatic skin of K5. hTGF β 1 transgenic mice. Exp. Dermatol. 2015 24 11 889 891 10.1111/exd.12779 26121067
    [Google Scholar]
  23. Cai B. Zheng Y. Ma S. Xing Q. Wang X. Yang B. Yin G. Guan F. Long non coding RNA regulates hair follicle stem cell proliferation and differentiation through PI3K/AKT signal pathway. Mol. Med. Rep. 2018 17 4 5477 5483 10.3892/mmr.2018.8546 29393477
    [Google Scholar]
  24. Mercurio L. Albanesi C. Madonna S. Recent updates on the involvement of PI3K/AKT/mTOR molecular cascade in the pathogenesis of hyperproliferative skin disorders. Front. Med. 2021 8 665647 10.3389/fmed.2021.665647 33996865
    [Google Scholar]
  25. Liang J. Slingerland J.M. Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression. Cell Cycle 2003 2 4 336 342 10.4161/cc.2.4.433 12851486
    [Google Scholar]
  26. Jiang N. Dai Q. Su X. Fu J. Feng X. Peng J. Role of PI3K/AKT pathway in cancer: The framework of malignant behavior. Mol. Biol. Rep. 2020 47 6 4587 4629 10.1007/s11033‑020‑05435‑1 32333246
    [Google Scholar]
  27. Irie H.Y. Pearline R.V. Grueneberg D. Hsia M. Ravichandran P. Kothari N. Natesan S. Brugge J.S. Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial–mesenchymal transition. J. Cell Biol. 2005 171 6 1023 1034 10.1083/jcb.200505087 16365168
    [Google Scholar]
  28. Murayama K. Kimura T. Tarutani M. Tomooka M. Hayashi R. Okabe M. Nishida K. Itami S. Katayama I. Nakano T. Akt activation induces epidermal hyperplasia and proliferation of epidermal progenitors. Oncogene 2007 26 33 4882 4888 10.1038/sj.onc.1210274 17297448
    [Google Scholar]
  29. Yang Z. Yin X. Chen C. Huang S. Li X. Yan J. Sun Q. CircOAS3 regulates keratinocyte proliferation and psoriatic inflammation by interacting with Hsc70 via the JNK/STAT3/NF-κB signaling pathway. Inflammation 2022 45 5 1924 1935 10.1007/s10753‑022‑01664‑7 35307784
    [Google Scholar]
  30. Hammouda M. Ford A. Liu Y. Zhang J. The JNK signaling pathway in inflammatory skin disorders and cancer. Cells 2020 9 4 857 10.3390/cells9040857 32252279
    [Google Scholar]
  31. Kriehuber E. Bauer W. Charbonnier A.S. Winter D. Amatschek S. Tamandl D. Schweifer N. Stingl G. Maurer D. Balance between NF-κB and JNK/AP-1 activity controls dendritic cell life and death. Blood 2005 106 1 175 183 10.1182/blood‑2004‑08‑3072 15755895
    [Google Scholar]
  32. Luo J.L. Kamata H. Karin M. IKK/NF- B signaling: Balancing life and death - A new approach to cancer therapy. J. Clin. Invest. 2005 115 10 2625 2632 10.1172/JCI26322 16200195
    [Google Scholar]
  33. Moher D. Liberati A. Tetzlaff J. Altman D.G. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009 6 7 e1000097 10.1371/journal.pmed.1000097 19621072
    [Google Scholar]
  34. Lagunin A. Ivanov S. Rudik A. Filimonov D. Poroikov V. DIGEP-Pred: Web service for in silico prediction of drug-induced gene expression profiles based on structural formula. Bioinformatics 2013 29 16 2062 2063 10.1093/bioinformatics/btt322 23740741
    [Google Scholar]
  35. Szklarczyk D. Morris J.H. Cook H. Kuhn M. Wyder S. Simonovic M. Santos A. Doncheva N.T. Roth A. Bork P. Jensen L.J. von Mering C. The STRING database in 2017: Quality-controlled protein–protein association networks, made broadly accessible. Nucleic Acids Res. 2017 45 D1 D362 D368 10.1093/nar/gkw937 27924014
    [Google Scholar]
  36. Shannon P. Markiel A. Ozier O. Baliga N.S. Wang J.T. Ramage D. Amin N. Schwikowski B. Ideker T. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 2003 13 11 2498 2504 10.1101/gr.1239303 14597658
    [Google Scholar]
  37. Poroikov V.V. Filimonov D.A. Ihlenfeldt W.D. Gloriozova T.A. Lagunin A.A. Borodina Y.V. Stepanchikova A.V. Nicklaus M.C. PASS biological activity spectrum predictions in the enhanced open NCI database browser. J. Chem. Inf. Comput. Sci. 2003 43 1 228 236 10.1021/ci020048r 12546557
    [Google Scholar]
  38. Gao J. Guo J. Nong Y. Mo W. Fang H. Mi J. Qi Q. Yang M. 18β-Glycyrrhetinic acid induces human HaCaT keratinocytes apoptosis through ROS-mediated PI3K-Akt signaling pathway and ameliorates IMQ-induced psoriasis-like skin lesions in mice. BMC Pharmacol. Toxicol. 2020 21 1 41 10.1186/s40360‑020‑00419‑0 31900240
    [Google Scholar]
  39. Choi D.H. Hwang H.S. Anti-inflammation activity of brazilin in TNF-α induced human psoriasis dermatitis skin model. Appl. Biol. Chem. 2019 62 1 46 10.1186/s13765‑019‑0455‑z
    [Google Scholar]
  40. Leitner P.D. Jakschitz T. Gstir R. Stuppner S. Perkams S. Kruus M. Trockenbacher A. Griesbeck C. Bonn G.K. Huber L.A. Valovka T. Anti-inflammatory extract from soil algae Chromochloris zofingiensis targeting TNFR/NF-κB signaling at different levels. Cells 2022 11 9 1407 10.3390/cells11091407 35563717
    [Google Scholar]
  41. Takuathung M.N. Potikanond S. Sookkhee S. Mungkornasawakul P. Jearanaikulvanich T. Chinda K. Wikan N. Nimlamool W. Anti-psoriatic and anti-inflammatory effects of Kaempferia parviflora in keratinocytes and macrophage cells. Biomed. Pharmacother. 2021 143 112229 10.1016/j.biopha.2021.112229 34649355
    [Google Scholar]
  42. Peus D. Beyerle A. Pott M. Meves A. Pittelkow M.R. Rittner H.L. Weyand C. Anti-psoriatic drug anthralin activates JNK via lipid peroxidation: Mononuclear cells are more sensitive than keratinocytes. J. Invest. Dermatol. 2000 114 4 688 692 10.1046/j.1523‑1747.2000.00934.x 10733674
    [Google Scholar]
  43. Gao Y. Yuan J. Liang X. He Y. Li P. Yang M. Artemisia anomala extracts enhance the viability and anti-oxidation capacity of human keratinocytes. Trop. J. Pharm. Res. 2019 18 1 61 67 10.4314/tjpr.v18i1.10
    [Google Scholar]
  44. Dorjsembe B. Joo H. Nho C. Ham J. Kim J.C. Aruncus dioicus var. kamtschaticus extract ameliorates psoriasis-like skin inflammation via Akt/mTOR and JAK2/STAT3 signaling pathways in a murine model. Nutrients 2022 14 23 5094 10.3390/nu14235094 36501124
    [Google Scholar]
  45. Huang K.F. Ma K.H. Liu P.S. Chen B.W. Chueh S.H. Baicalein increases keratin 1 and 10 expression in HaCaT keratinocytes via TRPV 4 receptor activation. Exp. Dermatol. 2016 25 8 623 629 10.1111/exd.13024 27060689
    [Google Scholar]
  46. Bürger C. Shirsath N. Lang V. Diehl S. Kaufmann R. Weigert A. Han Y. Ringel C. Wolf P. Blocking mTOR signalling with rapamycin ameliorates imiquimod-induced psoriasis in mice. Acta Derm. Venereol. 2017 97 9 1087 1094 10.2340/00015555‑2724 28597024
    [Google Scholar]
  47. Nam Y.J. Lee C.S. Brefeldin A reduces tumor necrosis factor-α-stimulated production of inflammatory mediators by suppressing the Akt, mTOR, and NF-κB pathways in human keratinocytes. Naunyn Schmiedebergs Arch. Pharmacol. 2016 389 9 951 960 10.1007/s00210‑016‑1242‑6 27198515
    [Google Scholar]
  48. Blatt N. Boitano A. Lyssiotis C. Opipari A. Glick G. Bz-423 superoxide signals apoptosis via selective activation of JNK, Bak, and Bax. Free Radic. Biol. Med. 2008 45 9 1232 1242 10.1016/j.freeradbiomed.2008.07.022 18718527
    [Google Scholar]
  49. Liu A. Zhang B. Zhao W. Tu Y. Wang Q. Li J. Catalpol ameliorates psoriasis-like phenotypes via SIRT1 mediated suppression of NF-κB and MAPKs signaling pathways. Bioengineered 2021 12 1 183 195 10.1080/21655979.2020.1863015 33323018
    [Google Scholar]
  50. Liu A. Zhao W. Zhang B. Tu Y. Wang Q. Li J. Cimifugin ameliorates imiquimod-induced psoriasis by inhibiting oxidative stress and inflammation via NF-κB/MAPK pathway. Biosci. Rep. 2020 40 6 BSR20200471 10.1042/BSR20200471 32515468
    [Google Scholar]
  51. Ding Z. Liu J. Qian H. Wu L. Lv M. Cinnamaldehyde inhibits psoriasis like inflammation by suppressing proliferation and inflammatory response of keratinocytes via inhibition of NF κB and JNK signaling pathways. Mol. Med. Rep. 2021 24 3 638 10.3892/mmr.2021.12277 34278486
    [Google Scholar]
  52. Li C. Xiao L. Jia J. Li F. Wang X. Duan Q. Jing H. Yang P. Chen C. Wang Q. Liu J. Shao Y. Wang N. Zheng Y. Cornulin is induced in psoriasis lesions and promotes keratinocyte proliferation via phosphoinositide 3-kinase/Akt pathways. J. Invest. Dermatol. 2019 139 1 71 80 10.1016/j.jid.2018.06.184 30009832
    [Google Scholar]
  53. Cho J.W. Lee K.S. Kim C.W. Curcumin attenuates the expression of IL-1β, IL-6, and TNF-α as well as cyclin E in TNF-α-treated HaCaT cells; NF-κB and MAPKs as potential upstream targets. Int. J. Mol. Med. 2007 19 3 469 474 10.3892/ijmm.19.3.469 17273796
    [Google Scholar]
  54. Nguyen L.T.H. Ahn S.H. Nguyen U.T. Yang I.J. Dang-Gui-Liu-Huang Tang a traditional herbal formula, ameliorates imiquimod-induced psoriasis-like skin inflammation in mice by inhibiting IL-22 production. Phytomedicine 2018 47 48 57 10.1016/j.phymed.2018.04.051 30166108
    [Google Scholar]
  55. Gesser B. Rasmussen M.K. Raaby L. Rosada C. Johansen C. Kjellerup R.B. Kragballe K. Iversen L. Dimethylfumarate inhibits MIF-induced proliferation of keratinocytes by inhibiting MSK1 and RSK1 activation and by inducing nuclear p-c-Jun (S63) and p-p53 (S15) expression. Inflamm. Res. 2011 60 7 643 653 10.1007/s00011‑011‑0316‑7 21340650
    [Google Scholar]
  56. Shahine Y. El-Aal S.A.A. Reda A.M. Sheta E. Atia N.M. Abdallah O.Y. Ibrahim S.S.A. Diosmin nanocrystal gel alleviates imiquimod-induced psoriasis in rats via modulating TLR7,8/NF-κB/micro RNA-31, AKT/mTOR/P70S6K milieu, and Tregs/Th17 balance. Inflammopharmacology 2023 31 3 1341 1359 10.1007/s10787‑023‑01198‑w 37010718
    [Google Scholar]
  57. Wu J. Zhu R.D. Cao G.M. Du J.C. Liu X. Diao L.Z. Zhang Z.Y. Hu Y.S. Liu X.H. Shi J.B. Discovery of novel paeonol-based derivatives against skin inflammation in vitro and in vivo. J. Enzyme Inhib. Med. Chem. 2022 37 1 817 831 10.1080/14756366.2022.2043852 35220836
    [Google Scholar]
  58. Chamcheu J.C. Adhami V.M. Esnault S. Sechi M. Siddiqui I.A. Satyshur K.A. Syed D.N. Dodwad S.J.M. Chaves-Rodriquez M.I. Longley B.J. Wood G.S. Mukhtar H. Dual inhibition of PI3K/Akt and mTOR by the dietary antioxidant, delphinidin, ameliorates psoriatic features in vitro and in an imiquimod-induced psoriasis-like disease in mice. Antioxid. Redox Signal. 2017 26 2 49 69 10.1089/ars.2016.6769 27393705
    [Google Scholar]
  59. Roy T. Banang-Mbeumi S. Boateng S.T. Ruiz E.M. Chamcheu R.C.N. Kang L. King J.A. Walker A.L. Nagalo B.M. Kousoulas K.G. Esnault S. Huang S. Chamcheu J.C. Dual targeting of mTOR/IL-17A and autophagy by fisetin alleviates psoriasis-like skin inflammation. Front. Immunol. 2023 13 1075804 10.3389/fimmu.2022.1075804 36741386
    [Google Scholar]
  60. Mo C. Shetti D. Wei K. Erianin inhibits proliferation and induces apoptosis of HaCaT cells via ROS-mediated JNK/c-Jun and AKT/mTOR signaling pathways. Molecules 2019 24 15 2727 10.3390/molecules24152727 31357564
    [Google Scholar]
  61. Chamcheu J.C. Esnault S. Adhami V.M. Noll A.L. Banang-Mbeumi S. Roy T. Singh S.S. Huang S. Kousoulas K.G. Mukhtar H. Fisetin, a 3,7,3′,4′-Tetrahydroxyflavone inhibits the PI3K/Akt/mTOR and MAPK pathways and ameliorates psoriasis pathology in 2D and 3D organotypic human inflammatory skin models. Cells 2019 8 9 1089 10.3390/cells8091089 31540162
    [Google Scholar]
  62. Lu Y. Chen H. Zhang J. Tang B. Zhang H. Ma C. Tang X. Li L. Wu J. Wei J. Li S. Yang L. Han L. Lu C. Fuzhenghefuzhiyang formula (FZHFZY) improves epidermal differentiation via suppression of the Akt/mTORC1/S6K1 signalling pathway in psoriatic models. Front. Pharmacol. 2021 12 650816 10.3389/fphar.2021.650816 34456715
    [Google Scholar]
  63. Jia B. Luo X. Cheng F.W. Li L. Hu D.J. Wang F. Zhang S.Q. Gardiquimod inhibits the expression of calcium-induced differentiation markers in HaCaT cells. Mol. Biol. Rep. 2013 40 11 6363 6369 10.1007/s11033‑013‑2750‑9 24057248
    [Google Scholar]
  64. Fiechter R.H. de Jong H.M. van Mens L.J.J. Fluri I.A. Tas S.W. Baeten D.L.P. Yeremenko N.G. van de Sande M.G.H. IL-12p40/IL-23p40 blockade with ustekinumab decreases the synovial inflammatory infiltrate through modulation of multiple signaling pathways including MAPK-ERK and Wnt. Front. Immunol. 2021 12 611656 10.3389/fimmu.2021.611656 33746955
    [Google Scholar]
  65. Ip K. Song G. Banov D. Bassani A.S. Valdez B.C. In vitro evaluation of Naltrexone HCl 1% Topical Cream in XemaTop™ for psoriasis. Arch. Dermatol. Res. 2020 312 2 145 154 10.1007/s00403‑019‑01981‑2 31667579
    [Google Scholar]
  66. Jia H.Y. Qiu H.Y. Zhang M.D. Hou J.J. Zhou M.L. Wu Y. Lenalidomide attenuates IMQ-induced inflammation in a mouse model of psoriasis. Biomed. Pharmacother. 2022 156 113883 10.1016/j.biopha.2022.113883 36270258
    [Google Scholar]
  67. Koycheva I.K. Mihaylova L.V. Todorova M.N. Balcheva-Sivenova Z.P. Alipieva K. Ferrante C. Orlando G. Georgiev M.I. Leucosceptoside a from Devil’s Claw modulates psoriasis-like inflammation via suppression of the PI3K/AKT signaling pathway in keratinocytes. Molecules 2021 26 22 7014 10.3390/molecules26227014 34834106
    [Google Scholar]
  68. Xie X. Zhang L. Li X. Liu W. Wang P. Lin Y. Han X. Li P. Liangxue Jiedu formula improves psoriasis and dyslipidemia comorbidity via PI3K/Akt/mTOR pathway. Front. Pharmacol. 2021 12 591608 10.3389/fphar.2021.591608 33762935
    [Google Scholar]
  69. Lin Y. Zhu X. Li Y. Dou Y. Wang J. Qi R. Ma L. LY294002 ameliorates psoriatic skin inflammation in mice via blocking the Notch1/Hes1-PTEN/AKT/IL-17A feedback loop. Clin. Exp. Immunol. 2023 213 1 114 124 10.1093/cei/uxad025 36840628
    [Google Scholar]
  70. Guo J.W. Cheng Y.P. Liu C.Y. Thong H.Y. Lo Y. Wu C.Y. Jee S.H. Magnolol may contribute to barrier function improvement on imiquimod induced psoriasis like dermatitis animal model via the downregulation of interleukin 23. Exp. Ther. Med. 2021 21 5 448 10.3892/etm.2021.9876 33747183
    [Google Scholar]
  71. Nguyen U.T. Nguyen L.T.H. Kim B.A. Choi M.J. Yang I.J. Shin H.M. Natural compound mixture, containing emodin, genipin, chlorogenic acid, Cimigenoside, and Ginsenoside Rb1, ameliorates psoriasis‐like skin lesions by suppressing inflammation and proliferation in keratinocytes. Evid. Based Complement. Alternat. Med. 2020 2020 1 9416962 10.1155/2020/9416962 33149756
    [Google Scholar]
  72. Wikan N. Hankittichai P. Thaklaewphan P. Potikanond S. Nimlamool W. Oxyresveratrol inhibits TNF-α-stimulated cell proliferation in human immortalized keratinocytes (HaCaT) by suppressing AKT activation. Pharmaceutics 2021 14 1 63 10.3390/pharmaceutics14010063 35056961
    [Google Scholar]
  73. Tuure L. Hämälä, M.; Moilanen, E. PDE 4 inhibitor rolipram inhibits the expression of microsomal prostaglandin E synthase‐1 by a mechanism dependent on MAP kinase phosphatase‐1. Pharmacol. Res. Perspect. 2017 5 6 e00363 10.1002/prp2.363 29226622
    [Google Scholar]
  74. Wang X.L. Sun Q. Photodynamic therapy with 5-aminolevulinic acid suppresses IFN-γ-induced K17 expression in HaCaT cells via MAPK pathway. Eur. Rev. Med. Pharmacol. Sci. 2017 21 20 4694 4702 29131243
    [Google Scholar]
  75. Kanda N. Shibata S. Tada Y. Nashiro K. Tamaki K. Watanabe S. Prolactin enhances basal and IL‐17‐induced CCL20 production by human keratinocytes. Eur. J. Immunol. 2009 39 4 996 1006 10.1002/eji.200838852 19350575
    [Google Scholar]
  76. Yue L. Ailin W. Jinwei Z. Leng L. Jianan W. Li L. Haiming C. Ling H. Chuanjian L. PSORI-CM02 ameliorates psoriasis in vivo and in vitro by inducing autophagy via inhibition of the PI3K/Akt/mTOR pathway. Phytomedicine 2019 64 153054 10.1016/j.phymed.2019.153054 31401494
    [Google Scholar]
  77. Jeon Y.J. Kim B.H. Kim S. Oh I. Lee S. Shin J. Kim T.Y. Rhododendrin ameliorates skin inflammation through inhibition of NF-κB, MAPK, and PI3K/Akt signaling. Eur. J. Pharmacol. 2013 714 1-3 7 14 10.1016/j.ejphar.2013.05.041 23764465
    [Google Scholar]
  78. Jiang W.W. Wang Y.M. Wang X.Y. Zhang Q. Zhu S.M. Zhang C.L. Role and mechanism of matrine alone and combined with acitretin for HaCaT cells and psoriasis-like murine models. Chin. Med. J. 2019 132 17 2079 2088 10.1097/CM9.0000000000000412 31460901
    [Google Scholar]
  79. Zhang X. Li J. Yu Y. Lian P. Gao X. Xu Y. Geng L. Shikonin controls the differentiation of CD4+ CD25+ regulatory T cells by inhibiting AKT/mTOR pathway. Inflammation 2019 42 4 1215 1227 10.1007/s10753‑019‑00982‑7 31028576
    [Google Scholar]
  80. Zhao Y. Xie Y. Li X. Song J. Guo M. Xian D. Zhong J. The protective effect of proanthocyanidins on the psoriasis-like cell models via PI3K/AKT and HO-1. Redox Rep. 2022 27 1 200 211 10.1080/13510002.2022.2123841 36178125
    [Google Scholar]
  81. Chorachoo J. Lambert S. Furnholm T. Roberts L. Reingold L. Auepemkiate S. Voravuthikunchai S.P. Johnston A. The small molecule rhodomyrtone suppresses TNF-α and IL-17A-induced keratinocyte inflammatory responses: A potential new therapeutic for psoriasis. PLoS One 2018 13 10 e0205340 10.1371/journal.pone.0205340 30321197
    [Google Scholar]
  82. Lin Z.M. Ma M. Li H. Qi Q. Liu Y.T. Yan Y.X. Shen Y.F. Yang X.Q. Zhu F.H. He S.J. Tang W. Zuo J.P. Topical administration of reversible SAHH inhibitor ameliorates imiquimod-induced psoriasis-like skin lesions in mice via suppression of TNF-α/IFN-γ-induced inflammatory response in keratinocytes and T cell-derived IL-17. Pharmacol. Res. 2018 129 443 452 10.1016/j.phrs.2017.11.012 29155016
    [Google Scholar]
  83. Di T. Zhao J. Wang Y. Han L. Guo X. Han X. Chen Z. Li P. Lu C. Tuhuaiyin alleviates imiquimod-induced psoriasis via inhibiting the properties of IL-17-producing cells and remodels the gut microbiota. Biomed. Pharmacother. 2021 141 111884 10.1016/j.biopha.2021.111884 34243099
    [Google Scholar]
  84. Lv H. Liu X. Chen W. Xiao S. Ji Y. Han X. Li Y. Wang X. Zhang G. Li P. Yangxue jiedu fang ameliorates psoriasis by regulating vascular regression via Survivin/PI3K/Akt pathway. J. Immunol. Res. 2021 2021 1 1 18 10.1155/2021/4678087 33532507
    [Google Scholar]
  85. Lories R.J. Derese I. Luyten F.P. de Vlam K. Activation of nuclear factor kappa B and mitogen activated protein kinases in psoriatic arthritis before and after etanercept treatment. Clin. Exp. Rheumatol. 2008 26 1 96 102 18328153
    [Google Scholar]
  86. Huang H.S. Liu Z.M. Hong D.Y. Blockage of JNK pathway enhances arsenic trioxide-induced apoptosis in human keratinocytes. Toxicol. Appl. Pharmacol. 2010 244 2 234 241 10.1016/j.taap.2009.12.037 20074581
    [Google Scholar]
  87. Gazel A. Banno T. Walsh R. Blumenberg M. Inhibition of JNK promotes differentiation of epidermal keratinocytes. J. Biol. Chem. 2006 281 29 20530 20541 10.1074/jbc.M602712200 16648634
    [Google Scholar]
  88. Xue M. Chow S.O. Dervish S. Chan Y.K.A. Julovi S.M. Jackson C.J. Activated protein C enhances human keratinocyte barrier integrity via sequential activation of epidermal growth factor receptor and Tie2. J. Biol. Chem. 2011 286 8 6742 6750 10.1074/jbc.M110.181388 21173154
    [Google Scholar]
  89. Madonna S. Scarponi C. Pallotta S. Cavani A. Albanesi C. Anti-apoptotic effects of suppressor of cytokine signaling 3 and 1 in psoriasis. Cell Death Dis. 2012 3 e334 10.1038/cddis.2012.69
    [Google Scholar]
  90. Yoo J.A. Yu E. Park S.H. Oh S.W. Kwon K. Park S.J. Kim H. Yang S. Park J.Y. Cho J.Y. Kim Y.J. Lee J. Blue light irradiation induces human keratinocyte cell damage via transient receptor potential vanilloid 1 (TRPV1) regulation. Oxid. Med. Cell. Longev. 2020 2020 1 1 14 10.1155/2020/8871745 33381275
    [Google Scholar]
  91. Karakawa M. Komine M. Hanakawa Y. Tsuda H. Sayama K. Tamaki K. Ohtsuki M. CCL27 is downregulated by interferon gamma via epidermal growth factor receptor in normal human epidermal keratinocytes. J. Cell. Physiol. 2014 229 12 1935 1945 10.1002/jcp.24643 24710735
    [Google Scholar]
  92. Wang J. Li X. Zhang P. Yang T. Liu N. Qin L. CHRNA5 is overexpressed in patients with psoriasis and promotes psoriasis-like inflammation in mouse models. J. Invest. Dermatol. 2022 142 11 2978 2987.e6 10.1016/j.jid.2022.04.014 35513071
    [Google Scholar]
  93. Wu P. Ma G. Zhu X. Gu T. Zhang J. Sun Y. Xu H. Huo R. Wang B. Shen B. Chen X. Li N. Cyr61/CCN1 is involved in the pathogenesis of psoriasis vulgaris via promoting IL-8 production by keratinocytes in a JNK/NF-κB pathway. Clin. Immunol. 2017 174 53 62 10.1016/j.clim.2016.11.003 27856305
    [Google Scholar]
  94. Zhang B. Wu S. Downregulation of circ_0024028 inhibits IL-22-induced keratinocyte proliferation and migration by miR-486-3p/AKT3 axis. Arch. Dermatol. Res. 2023 315 7 2079 2090 10.1007/s00403‑023‑02597‑3 36943433
    [Google Scholar]
  95. Dallaglio K. Marconi A. Truzzi F. Lotti R. Palazzo E. Petrachi T. Saltari A. Coppini M. Pincelli C. E‐FABP induces differentiation in normal human keratinocytes and modulates the differentiation process in psoriatic keratinocytes in vitro. Exp. Dermatol. 2013 22 4 255 261 10.1111/exd.12111 23528210
    [Google Scholar]
  96. Mascia F. Cataisson C. Lee T.C. Threadgill D. Mariani V. Amerio P. Chandrasekhara C. Souto Adeva G. Girolomoni G. Yuspa S.H. Pastore S. EGFR regulates the expression of keratinocyte-derived granulocyte/macrophage colony-stimulating factor in vitro and in vivo. J. Invest. Dermatol. 2010 130 3 682 693 10.1038/jid.2009.336 19890352
    [Google Scholar]
  97. Zhuang L. Ma W. Yan J. Zhong H. Evaluation of the effects of IL-22 on the proliferation and differentiation of keratinocytes in vitro. Mol. Med. Rep. 2020 22 4 2715 2722 10.3892/mmr.2020.11348 32945375
    [Google Scholar]
  98. Wang H. Ran L-W. Hui K. Wang X-Y. Zheng Y. Expressions of survivin, PI3K and AKT in keratinocytes in skin lesions and their pathogenic role in psoriasis vulgaris. Nan Fang Yi Ke Da Xue Xue Bao 2017 37 11 1512 1516 10.3969/j.issn.1673‑4254.2017.11.14 29180333
    [Google Scholar]
  99. Liang J. Chen P. Li C. Li D. Wang J. Xue R. Zhang S. Ruan J. Zhang X. IL-22 down-regulates Cx43 expression and decreases gap junctional intercellular communication by activating the JNK pathway in psoriasis. J. Invest. Dermatol. 2019 139 2 400 411 10.1016/j.jid.2018.07.032 30171832
    [Google Scholar]
  100. Mitra A. Raychaudhuri S.K. Raychaudhuri S.P. IL-22 induced cell proliferation is regulated by PI3K/Akt/mTOR signaling cascade. Cytokine 2012 60 1 38 42 10.1016/j.cyto.2012.06.316 22840496
    [Google Scholar]
  101. Yin X. Yang Z. Zhu M. Chen C. Huang S. Li X. Zhong H. Wen H. Sun Q. Yu X. Yan J. ILF2 contributes to hyperproliferation of keratinocytes and skin inflammation in a KLHDC7B-DT-dependent manner in psoriasis. Front. Genet. 2022 13 890624 10.3389/fgene.2022.890624 35586566
    [Google Scholar]
  102. Rizaldy D. Toriyama M. Kato H. Fukui R. Fujita F. Nakamura M. Okada F. Morita A. Ishii K.J. Increase in primary cilia in the epidermis of patients with atopic dermatitis and psoriasis. Exp. Dermatol. 2021 30 6 792 803 10.1111/exd.14285 33455013
    [Google Scholar]
  103. Luo X. Jin R. Wang F. Jia B. Luan K. Cheng F.W. Li L. Sun L.D. Yang S. Zhang S.Q. Zhang X.J. Interleukin‐15 inhibits the expression of differentiation markers induced by Ca 2+ in keratinocytes. Exp. Dermatol. 2016 25 7 544 547 10.1111/exd.12992 26914593
    [Google Scholar]
  104. Tao Q. Huang H. Chai Y. Luo X. Zhang X. Jia B. Zhang S. Interleukin-6 up-regulates the expression of interleukin-15 is associated with MAPKs and PI3-K signaling pathways in the human keratinocyte cell line, HaCaT. Mol. Biol. Rep. 2012 39 4 4201 4205 10.1007/s11033‑011‑1205‑4 21769475
    [Google Scholar]
  105. Che D. Hang B. Li Y. Li K. Wang K. Wang H. Livin upregulation in keratinocytes of psoriasis patients to promote adhesion molecule expression. Int. J. Dermatol. 2023 62 7 900 909 10.1111/ijd.16621 36916467
    [Google Scholar]
  106. Tang Z.L. Zhang K. Lv S.C. Xu G.W. Zhang J.F. Jia H.Y. LncRNA MEG3 suppresses PI3K/AKT/mTOR signalling pathway to enhance autophagy and inhibit inflammation in TNF-α-treated keratinocytes and psoriatic mice. Cytokine 2021 148 155657 10.1016/j.cyto.2021.155657 34425525
    [Google Scholar]
  107. Kim D. Khin P.P. Lim O.K. Jun H.S. LPA/LPAR1 signaling induces PGAM1 expression via AKT/mTOR/HIF-1α pathway and increases aerobic glycolysis, contributing to keratinocyte proliferation Life. Sci 2022 311 Pt B 121201 10.1016/j.lfs.2022.121201 36400203
    [Google Scholar]
  108. Zheng Y. Cai B. Li X. Li D. Yin G. MiR-125b-5p and miR-181b-5p inhibit keratinocyte proliferation in skin by targeting Akt3. Eur. J. Pharmacol. 2019 862 172659 10.1016/j.ejphar.2019.172659 31518563
    [Google Scholar]
  109. Wang Y. Yu X. Wang L. Ma W. Sun Q. miR-320b is down-regulated in psoriasis and modulates keratinocyte proliferation by targeting AKT3. Inflammation 2018 41 6 2160 2170 10.1007/s10753‑018‑0859‑7 30136020
    [Google Scholar]
  110. Mercurio L. Morelli M. Scarponi C. Scaglione G.L. Pallotta S. Albanesi C. Madonna S. PI3Kδ sustains keratinocyte hyperproliferation and epithelial inflammation: implications for a topically druggable target in psoriasis. Cells 2021 10 10 2636 10.3390/cells10102636 34685616
    [Google Scholar]
  111. Tao T. Chen Y. Chen J. Lian C. Xu S. Zhang M. Fang C. PP2Acα regulates epidermal cell proliferation via the EGFR/AKT/mTOR pathway in psoriasis‐like skin lesions caused by PPP2CA deficiency Exp. Dermatol. 2022 31 8 exd.14567 10.1111/exd.14567 35298048
    [Google Scholar]
  112. Yu N. Zhang S. Lu J. Li Y. Yi X. Tang L. Su L. Ding Y. Serum amyloid A, an acute phase protein, stimulates proliferative and proinflammatory responses of keratinocytes. Cell Prolif. 2017 50 3 e12320 10.1111/cpr.12320 27910163
    [Google Scholar]
  113. Furue K. Ito T. Tanaka Y. Hashimoto-Hachiya A. Takemura M. Murata M. Kido-Nakahara M. Tsuji G. Nakahara T. Furue M. The EGFR-ERK/JNK-CCL20 pathway in scratched keratinocytes may underpin koebnerization in psoriasis patients. Int. J. Mol. Sci. 2020 21 2 434 10.3390/ijms21020434 31936670
    [Google Scholar]
  114. Afonina I.S. Van Nuffel E. Baudelet G. Driege Y. Kreike M. Staal J. Beyaert R. The paracaspase MALT 1 mediates CARD 14‐induced signaling in keratinocytes. EMBO Rep. 2016 17 6 914 927 10.15252/embr.201642109 27113748
    [Google Scholar]
  115. Kim Y. Lee J. Kim J. Choi C.W. Hwang Y.I. Kang J.S. Lee W.J. The pathogenic role of interleukin-22 and its receptor during UVB-induced skin inflammation. PLoS One 2017 12 5 e0178567 10.1371/journal.pone.0178567 28558005
    [Google Scholar]
  116. Ren Y. Dong H. Jin R. Jiang J. Zhang X. TRIM22 actives PI3K/Akt/mTOR pathway to promote psoriasis through enhancing cell proliferation and inflammation and inhibiting autophagy. Cutan. Ocul. Toxicol. 2022 41 4 304 309 10.1080/15569527.2022.2127750 36170453
    [Google Scholar]
  117. Zhang R. Wang Y.H. Shi X. Ji J. Zhan F.Q. Leng H. Sortilin regulates keratinocyte proliferation and apoptosis through the PI3K-AKT signaling pathway. Life Sci. 2021 278 119630 10.1016/j.lfs.2021.119630 34004257
    [Google Scholar]
  118. Yu X.J. Li C.Y. Xu Y.H. Chen L.M. Zhou C.L. Calcitonin gene‐related peptide increases proliferation of human HaCaT keratinocytes by activation of MAP kinases. Cell Biol. Int. 2009 33 11 1144 1148 10.1016/j.cellbi.2009.07.003 19651223
    [Google Scholar]
  119. Han Y.H. Feng L. Lee S.J. Zhang Y.Q. Wang A.G. Jin M.H. Sun H.N. Kwon T. Depletion of peroxiredoxin II promotes keratinocyte apoptosis and alleviates psoriatic skin lesions via the PI3K/AKT/GSK3β signaling axis. Cell Death Discov. 2023 9 1 263 10.1038/s41420‑023‑01566‑z 37500620
    [Google Scholar]
  120. Sun R. Liu C. Liu J. Yin S. Song R. Ma J. Cao G. Lu Y. Zhang G. Wu Z. Chen A. Wang Y. Integrated network pharmacology and experimental validation to explore the mechanisms underlying naringenin treatment of chronic wounds. Sci. Rep. 2023 13 1 132 10.1038/s41598‑022‑26043‑y 36599852
    [Google Scholar]
  121. Ranjbar S. Mohammadi P. Pashaei S. Sadeghi M. Mehrabi M. Shabani S. Ebrahimi A. Brühl A.B. Khodarahmi R. Brand S. Effect of Aflatoxin B1 on the nervous system: A systematic review and network analysis highlighting Alzheimer’s disease. Biology 2025 14 4 436 10.3390/biology14040436 40282301
    [Google Scholar]
  122. Simmons D.L. What makes a good anti-inflammatory drug target? Drug Discov. Today 2006 11 5-6 210 219 10.1016/S1359‑6446(05)03721‑9 16580598
    [Google Scholar]
  123. Kong P. Cui Z.Y. Huang X.F. Zhang D.D. Guo R.J. Han M. Inflammation and atherosclerosis: Signaling pathways and therapeutic intervention. Signal Transduct. Target. Ther. 2022 7 1 131 10.1038/s41392‑022‑00955‑7 35459215
    [Google Scholar]
  124. Mahesh G. Anil Kumar K. Reddanna P. Overview on the discovery and development of anti-inflammatory drugs: Should the focus Be on synthesis or degradation of PGE2? J. Inflamm. Res. 2021 14 253 263 10.2147/JIR.S278514 33568930
    [Google Scholar]
  125. Conrad C. Gilliet M. Psoriasis: From pathogenesis to targeted therapies. Clin. Rev. Allergy Immunol. 2018 54 1 102 113 10.1007/s12016‑018‑8668‑1 29349534
    [Google Scholar]
  126. Vičić M. Kaštelan M. Brajac I. Sotošek V. Massari L.P. Current concepts of psoriasis immunopathogenesis. Int. J. Mol. Sci. 2021 22 21 11574 10.3390/ijms222111574 34769005
    [Google Scholar]
  127. Reich K. Armstrong A.W. Foley P. Song M. Wasfi Y. Randazzo B. Li S. Shen Y.K. Gordon K.B. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-blind, placebo- and active comparator–controlled VOYAGE 2 trial. J. Am. Acad. Dermatol. 2017 76 3 418 431 10.1016/j.jaad.2016.11.042 28057361
    [Google Scholar]
  128. Merola J.F. Landewé R. McInnes I.B. Mease P.J. Ritchlin C.T. Tanaka Y. Asahina A. Behrens F. Gladman D.D. Gossec L. Gottlieb A.B. Thaçi D. Warren R.B. Ink B. Assudani D. Bajracharya R. Shende V. Coarse J. Coates L.C. Bimekizumab in patients with active psoriatic arthritis and previous inadequate response or intolerance to tumour necrosis factor-α inhibitors: A randomised, double-blind, placebo-controlled, phase 3 trial (BE COMPLETE). Lancet 2023 401 10370 38 48 10.1016/S0140‑6736(22)02303‑0 36495881
    [Google Scholar]
  129. Griffiths C.E.M. Armstrong A.W. Gudjonsson J.E. Barker J.N.W.N. Psoriasis. Lancet 2021 397 10281 1301 1315 10.1016/S0140‑6736(20)32549‑6 33812489
    [Google Scholar]
  130. Psoriasis L.M. Psoriasis. Ann. Intern. Med. 2018 168 7 Itc49 itc64 10.7326/AITC201804030 29610923
    [Google Scholar]
  131. Lee P.W. Smith A.J. Yang Y. Selhorst A.J. Liu Y. Racke M.K. Lovett-Racke A.E. IL-23R–activated STAT3/STAT4 is essential for Th1/Th17-mediated CNS autoimmunity. JCI Insight 2017 2 17 e91663 10.1172/jci.insight.91663 28878115
    [Google Scholar]
  132. Xie Y. Li X. Ge J. STAT3–CyPA signaling pathway in endothelial cell apoptosis. Cell. Signal. 2020 65 109413 10.1016/j.cellsig.2019.109413 31494257
    [Google Scholar]
  133. Yang W. Bai X. Jia X. Li H. Min J. Li H. Zhang H. Zhou J. Zhao Y. Liu W. Xin H. Sun L. The binding of extracellular cyclophilin A to ACE2 and CD147 triggers psoriasis-like inflammation. J. Autoimmun. 2024 148 103293 10.1016/j.jaut.2024.103293 39096717
    [Google Scholar]
  134. Lu H. Kuang Y.H. Su J. Chang J. Wu L.S. Kanekura T. Li D. Chen M.L. Chen X. CD147 is highly expressed on peripheral blood neutrophils from patients with psoriasis and induces neutrophil chemotaxis. J. Dermatol. 2010 37 12 1053 1056 10.1111/j.1346‑8138.2010.00935.x 21083710
    [Google Scholar]
  135. Peng C. Zhang S. Lei L. Zhang X. Jia X. Luo Z. Huang X. Kuang Y. Zeng W. Su J. Chen X. Epidermal CD147 expression plays a key role in IL-22-induced psoriatic dermatitis. Sci. Rep. 2017 7 1 44172 10.1038/srep44172 28272440
    [Google Scholar]
  136. Okubo A. Uchida Y. Higashi Y. Sato T. Ogawa Y. Ryuge A. Kadomatsu K. Kanekura T. CD147 is essential for the development of psoriasis via the induction of Th17 cell differentiation. Int. J. Mol. Sci. 2021 23 1 177 10.3390/ijms23010177 35008603
    [Google Scholar]
  137. Calautti E. Avalle L. Poli V. Psoriasis: A STAT3-Centric view. Int. J. Mol. Sci. 2018 19 1 171 10.3390/ijms19010171 29316631
    [Google Scholar]
  138. Hou Y. Zhu L. Tian H. Sun H.X. Wang R. Zhang L. Zhao Y. IL-23-induced macrophage polarization and its pathological roles in mice with imiquimod-induced psoriasis. Protein Cell 2018 9 12 1027 1038 10.1007/s13238‑018‑0505‑z 29508278
    [Google Scholar]
  139. Kishimoto M. Komine M. Sashikawa-Kimura M. Ansary T.M. Kamiya K. Sugai J. Mieno M. Kawata H. Sekimoto R. Fukushima N. Ohtsuki M. STAT3 activation in psoriasis and cancers. Diagnostics 2021 11 10 1903 10.3390/diagnostics11101903 34679602
    [Google Scholar]
  140. Sano S. Chan K.S. Carbajal S. Clifford J. Peavey M. Kiguchi K. Itami S. Nickoloff B.J. DiGiovanni J. Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nat. Med. 2005 11 1 43 49 10.1038/nm1162 15592573
    [Google Scholar]
  141. Zhan Y.P. Chen B.S. Drug target identification and drug repurposing in psoriasis through systems biology approach, DNN-based DTI model and genome-wide microarray data. Int. J. Mol. Sci. 2023 24 12 10033 10.3390/ijms241210033 37373186
    [Google Scholar]
  142. Du Z. Lovly C.M. Mechanisms of receptor tyrosine kinase activation in cancer. Mol. Cancer 2018 17 1 58 10.1186/s12943‑018‑0782‑4 29455648
    [Google Scholar]
  143. Sudhesh Dev S. Farghadani R. Zainal Abidin S.A. Othman I. Naidu R. Flavonoids as receptor tyrosine kinase inhibitors in lung cancer. J. Funct. Foods 2023 110 105845 10.1016/j.jff.2023.105845
    [Google Scholar]
  144. Lemmon M.A. Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell 2010 141 7 1117 1134 10.1016/j.cell.2010.06.011 20602996
    [Google Scholar]
  145. Chen Z. Tian D. Liao X. Zhang Y. Xiao J. Chen W. Liu Q. Chen Y. Li D. Zhu L. Cai S. Apigenin combined with gefitinib blocks autophagy flux and induces apoptotic cell death through inhibition of HIF-1α, c-Myc, p-EGFR, and glucose metabolism in EGFR L858R+T790M-mutated H1975 cells. Front. Pharmacol. 2019 10 260 10.3389/fphar.2019.00260 30967777
    [Google Scholar]
  146. Ganthala P.D. Alavala S. Chella N. Andugulapati S.B. Bathini N.B. Sistla R. Co-encapsulated nanoparticles of Erlotinib and Quercetin for targeting lung cancer through nuclear EGFR and PI3K/AKT inhibition. Colloids Surf. B Biointerfaces 2022 211 112305 10.1016/j.colsurfb.2021.112305 34998178
    [Google Scholar]
  147. Park J.B. Park H. Son J. Ha S-J. Cho H-S. Structural study of monomethyl fumarate-bound human GAPDH. Mol. Cells 2019 42 8 597 603 10.14348/molcells.2019.0114 31387164
    [Google Scholar]
  148. Kornberg M.D. Bhargava P. Kim P.M. Putluri V. Snowman A.M. Putluri N. Calabresi P.A. Snyder S.H. Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity. Science 2018 360 6387 449 453 10.1126/science.aan4665 29599194
    [Google Scholar]
  149. Glaviano A. Foo A.S.C. Lam H.Y. Yap K.C.H. Jacot W. Jones R.H. Eng H. Nair M.G. Makvandi P. Geoerger B. Kulke M.H. Baird R.D. Prabhu J.S. Carbone D. Pecoraro C. Teh D.B.L. Sethi G. Cavalieri V. Lin K.H. Javidi-Sharifi N.R. Toska E. Davids M.S. Brown J.R. Diana P. Stebbing J. Fruman D.A. Kumar A.P. PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer. Mol. Cancer 2023 22 1 138 10.1186/s12943‑023‑01827‑6 37596643
    [Google Scholar]
  150. Liu T. Zhang L. Joo D. Sun S.C. NF-κB signaling in inflammation. Signal Transduct. Target. Ther. 2017 2 1 17023 10.1038/sigtrans.2017.23 29158945
    [Google Scholar]
  151. Tang W. Long T. Li F. Peng C. Zhao S. Chen X. Su J. HIF-1α may promote glycolysis in psoriasis vulgaris via upregulation of CD147 and GLUT1. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 46 4 333 344 10.11817/j.issn.1672‑7347.2021.200010 33967078
    [Google Scholar]
  152. Wang D. Liu G. Meng Y. Chen H. Ye Z. Jing J. The configuration of GRB2 in protein interaction and signal transduction. Biomolecules 2024 14 3 259 10.3390/biom14030259 38540680
    [Google Scholar]
  153. Frelin C. Ofran Y. Ruston J. Hayun M. Derdikman Y. Khier Y. Rozales K. Brenner B. Iscove N. Pawson T. Louria-Hayon I. Grb2 regulates the proliferation of hematopoietic stem and progenitors cells. Biochim. Biophys. Acta Mol. Cell Res. 2017 1864 12 2449 2459 10.1016/j.bbamcr.2017.09.018 28964849
    [Google Scholar]
  154. Bakry O.A. Samaka R.M. Shoeib M.A.M. Abdel Aal S.M. Nuclear factor kappa B and cyclo-oxygenase-2: Two concordant players in psoriasis pathogenesis. Ultrastruct. Pathol. 2015 39 1 49 61 10.3109/01913123.2014.952470 25215902
    [Google Scholar]
  155. Thomas G.J. Herranz P. Cruz S.B. Parodi A. Treatment of actinic keratosis through inhibition of cyclooxygenase‐2: Potential mechanism of action of diclofenac sodium 3% in hyaluronic acid 2.5%. Dermatol. Ther. 2019 32 3 e12800 10.1111/dth.12800 30523664
    [Google Scholar]
/content/journals/cpb/10.2174/0113892010380506250909114143
Loading
Exploring the Interplay of PI3K/AKT/mTOR and JNK Signaling Pathways in Psoriasis: Insights from Systematic Review and Network Pharmacology Approach
Bentham Science Publishers ; https://doi.org/10.2174/0113892010380506250909114143
/content/journals/cpb/10.2174/0113892010380506250909114143
/content/journals/cpb/10.2174/0113892010380506250909114143
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.

file format download Download

  • Article Type:     Review Article
Keywords: Psoriasis ; PI3K/AKT/mTOR ; inflammation ; JNK ; signaling pathway ; flavonoids

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test