Skip to content
2000
Volume 25, Issue 12
  • ISSN: 1566-5240
  • E-ISSN: 1875-5666

Abstract

Background

The transcription factor AP1 plays a crucial role in the proliferation, apoptosis, and terminal differentiation of epidermal keratinocytes.

Objective

This study aimed to clarify whether the subunit of AP1, FOSL1 protein, can be used to assess the exacerbation of psoriasis by evaluating its changes in protein and mRNA levels in cultured epidermal keratinocytes and skin specimens of the patients prescribed with bathwater PUVA (Psoralen and UVA) therapy. This study aimed to investigate FOSL1, a subunit of the transcription factor AP-1, as a potential biomarker for psoriasis by examining its protein and mRNA expression in skin specimens from patients undergoing bathwater PUVA (Psoralen and UVA) therapy and cultured epidermal keratinocytes.

Methods

The distribution of FOSL1 in patients’ skin was explored by immunohistochemistry. Changes in gene and protein expression were quantitatively assessed by qPCR and ELISA, respectively.

Results

Immunohistochemistry analysis revealed that FOSL1 accumulated in lesional skin. The expression of FOSL1 significantly increased during disease flare-ups but decreased following the treatment with bathwater PUVA therapy. Furthermore, silencing FOSL1 led to a marked reduction in the expression of ten FOSL1 target genes associated with the disease.

Conclusion

Our study suggests that FOSL1 shows potential as a biomarker for psoriasis. This is supported by two key findings: first, the expression of FOSL1 correlates with disease activity, and second, its expression is linked to changes in the expression of genes previously implicated in the pathogenesis of psoriasis, namely , , , , , , , , and .

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmm/10.2174/0115665240343441241231102305
2025-01-17
2025-12-20

  • From This Site

    /content/journals/cmm/10.2174/0115665240343441241231102305
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. HuP. WangM. GaoH. The role of helper T cells in psoriasis.Front. Immunol.20211278894010.3389/fimmu.2021.788940 34975883
     [Google Scholar]
  2. PouraniM.R. AbdollahimajdF. ZargariO. Shahidi DadrasM. Soluble biomarkers for diagnosis, monitoring, and therapeutic response assessment in psoriasis.J. Dermatolog. Treat.20223341967197410.1080/09546634.2021.1966357 34369253
     [Google Scholar]
  3. GelfandJ.M. ShinD.B. AlaviA. A phase IV, randomized, double-blind, placebo-controlled crossover study of the effects of ustekinumab on vascular inflammation in psoriasis (the VIP-U trial).J. Invest. Dermatol.202014018593.e210.1016/j.jid.2019.07.679 31326395
     [Google Scholar]
  4. RichardM.A. PaulC. NijstenT. Prevalence of most common skin diseases in Europe: A population‐based study.J. Eur. Acad. Dermatol. Venereol.20223671088109610.1111/jdv.18050 35274366
     [Google Scholar]
  5. ArmstrongA.W. MehtaM.D. SchuppC.W. GondoG.C. BellS.J. GriffithsC.E.M. Psoriasis prevalence in adults in the United States.JAMA Dermatol.2021157894094610.1001/jamadermatol.2021.2007 34190957
     [Google Scholar]
  6. ParisiR. IskandarI.Y.K. KontopantelisE. AugustinM. GriffithsC.E.M. AshcroftD.M. National, regional, and worldwide epidemiology of psoriasis: systematic analysis and modelling study.BMJ2020369m159010.1136/bmj.m1590 32467098
     [Google Scholar]
  7. MukhamadeevaO.R. SharafutdinovaN.K. SaitovaZ.R. The dynamic and structural indicators of population morbidity of diseases of skin and subcutaneous fat: The scientific review.Probl. Sotsialnoi Gig. Istor. Med.20233161313132210.32687/0869‑866X‑2023‑31‑6‑1313‑1322 38142329
     [Google Scholar]
  8. KaushikS.B. LebwohlM.G. Psoriasis: Which therapy for which patient.J. Am. Acad. Dermatol.2019801274010.1016/j.jaad.2018.06.057 30017705
     [Google Scholar]
  9. CoscarellaG. FalcoG.M. PalmisanoG. Low grade of satisfaction related to the use of current systemic therapies among pustular psoriasis patients: A therapeutic unmet need to be fulfilled.Front. Med. (Lausanne)202410129597310.3389/fmed.2023.1295973 38274451
     [Google Scholar]
  10. ArmstrongA.W. ReadC. Pathophysiology, clinical presentation, and treatment of psoriasis: A review.JAMA2020323191945196010.1001/jama.2020.4006 32427307
     [Google Scholar]
  11. LeeH.J. KimM. Challenges and future trends in the treatment of psoriasis.Int. J. Mol. Sci.202324171331310.3390/ijms241713313 37686119
     [Google Scholar]
  12. SobolevV.V. KhashukoevaA.Z. EvinaO.E. Role of the transcription factor FOSL1 in organ development and tumorigenesis.Int. J. Mol. Sci.2022233152110.3390/ijms23031521 35163444
     [Google Scholar]
  13. Aghaei-ZarchS.M. NiaA.H.S. NouriM. The impact of particulate matters on apoptosis in various organs: Mechanistic and therapeutic perspectives.Biomed. Pharmacother.202316511505410.1016/j.biopha.2023.115054 37379642
     [Google Scholar]
  14. MogulevtsevaJ.A. MezentsevA.V. BruskinS.A. Impact of metalloproteinase 1 deficiency induced by specific small hairpin RNA on the physiological effects of tumor necrosis factor.Russ. J. Genet.201854896096610.1134/S1022795418080094
     [Google Scholar]
  15. MogulevtsevaJ.A. MezentsevA.V. BruskinS.A. RNAi-mediated silencing of matrix metalloproteinase 1 in epidermal keratinocytes influences the biological effects of interleukin 17A.Vavilovskii Zhurnal Genet. Selektsii201822442543210.18699/VJ18.378
     [Google Scholar]
  16. MogulevtsevaJ.A. MezentsevA.V. BruskinS.A. Changes caused by MMP1-silencing in epidermal keratinocytes pretreated with interferon-γ and their analysis.Mol Appl Genetics201723102109
     [Google Scholar]
  17. YaoY. RichmanL. MorehouseC. Type I interferon: Potential therapeutic target for psoriasis?PLoS One200837e273710.1371/journal.pone.0002737 18648529
     [Google Scholar]
  18. CasalinoL. TalottaF. MatinoI. VerdeP. FRA-1 as a regulator of EMT and metastasis in breast cancer.Int. J. Mol. Sci.2023249830710.3390/ijms24098307 37176013
     [Google Scholar]
  19. SobolevV.V. ZolotarenkoA.D. SobolevaA.G. Expression of the FOSL1 gene in psoriasis and atherosclerosis.Genetika2010461104110 20198886
     [Google Scholar]
  20. ZengF. LiuH. LuD. LiuQ. ChenH. ZhengF. Integrated analysis of gene expression profiles identifies transcription factors potentially involved in psoriasis pathogenesis.J. Cell. Biochem.20191208125821259410.1002/jcb.28525 30825251
     [Google Scholar]
  21. LiangY. HanD. ZhangS. SunL. FOSL1 regulates hyperproliferation and NLRP3-mediated inflammation of psoriatic keratinocytes through the NF-kB signaling via transcriptionally activating TRAF3.Biochim. Biophys. Acta Mol. Cell Res.20241871411968910.1016/j.bbamcr.2024.119689 38367916
     [Google Scholar]
  22. ChenX. DengG. ChenK. ChenY. YeW. SunP. Targeting the NLRP3 inflammasome in psoriasis.Int. J. Dermatol.202463784485110.1111/ijd.17073 38345734
     [Google Scholar]
  23. LinQ. LiS. JiangN. Inhibiting NLRP3 inflammasome attenuates apoptosis in contrast-induced acute kidney injury through the upregulation of HIF1A and BNIP3-mediated mitophagy.Autophagy202117102975299010.1080/15548627.2020.1848971 33345685
     [Google Scholar]
  24. LinM. JiX. LvY. CuiD. XieJ. The roles of TRAF3 in immune responses.Dis. Markers2023202311110.1155/2023/7787803 36845015
     [Google Scholar]
  25. HornickE.L. BishopG.A. TRAF3: Guardian of T lymphocyte functions.Front. Immunol.202314112925110.3389/fimmu.2023.1129251 36814922
     [Google Scholar]
  26. ZhouX. ChenY. CuiL. ShiY. GuoC. Advances in the pathogenesis of psoriasis: From keratinocyte perspective.Cell Death Dis.20221318110.1038/s41419‑022‑04523‑3 35075118
     [Google Scholar]
  27. ZhangZ. LiuL. ShenY. Characterization of chromatin accessibility in psoriasis.Front. Med.202216348349510.1007/s11684‑021‑0872‑3 34669155
     [Google Scholar]
  28. SobolevV. NesterovaA. SobolevaA. Analysis of PPARγ signaling activity in psoriasis.Int. J. Mol. Sci.20212216860310.3390/ijms22168603 34445309
     [Google Scholar]
  29. BenhadouF. GlitznerE. BrisebarreA. Epidermal autonomous VEGFA/Flt1/Nrp1 functions mediate psoriasis-like disease.Sci. Adv.202062eaax584910.1126/sciadv.aax5849 31934626
     [Google Scholar]
  30. MezentsevA. DurymanovM. MakarovV.A. A Comprehensive Review of Protein Biomarkers for Invasive Lung Cancer.Curr. Oncol.20243194818485410.3390/curroncol31090360 39329988
     [Google Scholar]
  31. Calzavara-PintonP. ArisiM. TononF. Calzavara-PintonI. VenturiniM. RossiM. Bath‐PUVA still represents a valuable treatment option for the subsets of psoriatic patients who are not eligible to or rejecting systemic treatments and are not responsive to NB‐UVB phototherapy.Photodermatol. Photoimmunol. Photomed.202339435135610.1111/phpp.12846 36398948
     [Google Scholar]
  32. NischalU. NischalK.C. KhopkarU. Techniques of skin biopsy and practical considerations.J. Cutan. Aesthet. Surg.20081210711110.4103/0974‑2077.44174 20300359
     [Google Scholar]
  33. FeldmanS.R. KruegerG.G. Psoriasis assessment tools in clinical trials.Ann. Rheum. Dis.200564Suppl. 2ii65ii6810.1136/ard.2004.031237 15708941
     [Google Scholar]
  34. PrelovskayaA. MezentsevA. PiruzianE. SobolevaA. BruskinS. Silencing the transcription factor FOSL1 in hyperproliferative HaCaT cells makes them susceptible to IFN-γ.Immunol. Endocr. Metab. Agents Med. Chem.2016163199209
     [Google Scholar]
  35. LivakK.J. SchmittgenT.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)).Method. Methods200125440240810.1006/meth.2001.1262 11846609
     [Google Scholar]
  36. KeselmanH.J. RoganJ.C. The Tukey multiple comparison test: 1953-1976.Psychol. Bull.19778451050105610.1037/0033‑2909.84.5.1050
     [Google Scholar]
  37. TchernitsaO.I. SersC. ZuberJ. Transcriptional basis of KRAS oncogene-mediated cellular transformation in ovarian epithelial cells.Oncogene200423264536455510.1038/sj.onc.1207585 15064704
     [Google Scholar]
  38. EckertR.L. AdhikaryG. YoungC.A. AP1 transcription factors in epidermal differentiation and skin cancer.J. Skin Cancer201320131910.1155/2013/537028 23762562
     [Google Scholar]
  39. RangarajA. YeL. SandersA.J. PriceP.E. HardingK.G. JiangW.G. Molecular and cellular impact of Psoriasin (S100A7) on the healing of human wounds.Exp. Ther. Med.20171352151216010.3892/etm.2017.4275 28565822
     [Google Scholar]
  40. Stelniec-KlotzI. LegewieS. TchernitsaO. Reverse engineering a hierarchical regulatory network downstream of oncogenic KRAS.Mol. Syst. Biol.20128160110.1038/msb.2012.32 22864383
     [Google Scholar]
  41. BakiriL. Macho-MaschlerS. CusticI. Fra-1/AP-1 induces EMT in mammary epithelial cells by modulating Zeb1/2 and TGFβ expression.Cell Death Differ.201522233635010.1038/cdd.2014.157 25301070
     [Google Scholar]
  42. MachinoH. DozenA. KonakaM. Integrative analysis reveals early epigenetic alterations in high-grade serous ovarian carcinomas.Exp. Mol. Med.202355102205221910.1038/s12276‑023‑01090‑1 37779141
     [Google Scholar]
  43. DieschJ. SanijE. GilanO. Widespread FRA1-dependent control of mesenchymal transdifferentiation programs in colorectal cancer cells.PLoS One201493e8895010.1371/journal.pone.0088950 24658684
     [Google Scholar]
  44. SobolevaA.G. BruskinS.A. NikolaevA.A. SobolevV.V. MezentsevA.V. Role of receptor for advanced glycation end-products in pathgenesis of psoriasis.Mol. Biol.2013475743753 25509346
     [Google Scholar]
  45. DongH. ZhangY. HuangY. DengH. Pathophysiology of RAGE in inflammatory diseases.Front. Immunol.20221393147310.3389/fimmu.2022.931473 35967420
     [Google Scholar]
  46. TakadaY. MatsuoK. Gefitinib, but not erlotinib, is a possible inducer of Fra-1-mediated interstitial lung disease.Keio J. Med.201261412012710.2302/kjm.2011‑0009‑OA 23324306
     [Google Scholar]
  47. CasalinoL. BakiriL. TalottaF. Fra-1 promotes growth and survival in RAS-transformed thyroid cells by controlling cyclin A transcription.EMBO J.20072671878189010.1038/sj.emboj.7601617 17347653
     [Google Scholar]
  48. LauE.Y.T. LoJ. ChengB.Y.L. Cancer-associated fibroblasts regulate tumor-initiating cell plasticity in hepatocellular carcinoma through c- Met/FRA1/HEY1 signaling.Cell Rep.20161561175118910.1016/j.celrep.2016.04.019 27134167
     [Google Scholar]
  49. VazM. MachireddyN. IrvingA. Oxidant-induced cell death and Nrf2-dependent antioxidative response are controlled by Fra-1/AP-1.Mol. Cell. Biol.20123291694170910.1128/MCB.06390‑11 22393254
     [Google Scholar]
  50. NaT.Y. KimG.H. OhH.J. The trisaccharide raffinose modulates epidermal differentiation through activation of liver X receptor.Sci. Rep.2017714382310.1038/srep43823 28266648
     [Google Scholar]
  51. WuJ. JiA. WangX. MicroRNA-195-5p, a new regulator of Fra-1, suppresses the migration and invasion of prostate cancer cells.J. Transl. Med.201513128910.1186/s12967‑015‑0650‑6 26337460
     [Google Scholar]
  52. Moquet-TorcyG. TolzaC. PiechaczykM. Jariel-EncontreI. Transcriptional complexity and roles of Fra-1/AP-1 at the uPA/Plau locus in aggressive breast cancer.Nucleic Acids Res.20144217110111102410.1093/nar/gku814 25200076
     [Google Scholar]
  53. MartinE.C. KrebsA.E. BurksH.E. miR-155 induced transcriptome changes in the MCF-7 breast cancer cell line leads to enhanced mitogen activated protein kinase signaling.Genes Cancer201459-1035336410.18632/genesandcancer.33 25352952
     [Google Scholar]
  54. RamachandranA. RanpuraS.A. GongE.M. MuloneM. CannonG.M. AdamR.M. An Akt- and Fra-1-dependent pathway mediates platelet-derived growth factor-induced expression of thrombomodulin, a novel regulator of smooth muscle cell migration.Am. J. Pathol.2010177111913110.2353/ajpath.2010.090772 20472895
     [Google Scholar]
  55. BurchP.M. YuanZ. LoonenA. HeintzN.H. An extracellular signal-regulated kinase 1- and 2-dependent program of chromatin trafficking of c-Fos and Fra-1 is required for cyclin D1 expression during cell cycle reentry.Mol. Cell. Biol.200424114696470910.1128/MCB.24.11.4696‑4709.2004 15143165
     [Google Scholar]
  56. ZhuW. LiJ. SuJ. FOS-like antigen 1 is highly expressed in human psoriasis tissues and promotes the growth of HaCaT cells in vitro.Mol. Med. Rep.20141052489249410.3892/mmr.2014.2509 25175497
     [Google Scholar]
  57. HoyS.M. Patisiran: First global approval.Drugs201878151625163110.1007/s40265‑018‑0983‑6 30251172
     [Google Scholar]
  58. SyedY.Y. Givosiran: A review in acute hepatic Porphyria.Drugs202181784184810.1007/s40265‑021‑01511‑3 33871817
     [Google Scholar]
  59. D’AmbrosioV. FerraroP.M. Lumasiran in the management of patients with primary hyperoxaluria type 1: from bench to bedside.Int. J. Nephrol. Renovasc. Dis.20221519720610.2147/IJNRD.S293682 35747094
     [Google Scholar]
  60. LambY.N. Inclisiran: First approval.Drugs202181338939510.1007/s40265‑021‑01473‑6 33620677
     [Google Scholar]
  61. GangwarR.S. GudjonssonJ.E. WardN.L. Mouse models of psoriasis: A comprehensive review.J. Invest. Dermatol.20221423 Pt B88489710.1016/j.jid.2021.06.019 34953514
     [Google Scholar]
  62. SobolevaA.G. MezentsevA.V. BruskinS.A. [Genetically modified animals as model systems of psoriasis].Mol Biol2014484587599 25842844
     [Google Scholar]
/content/journals/cmm/10.2174/0115665240343441241231102305
Loading
Using the AP1 Transcription Factor FOSL1 to Assess the Exacerbation of Psoriasis
Current Molecular Medicine 25, 1534 (2025); https://doi.org/10.2174/0115665240343441241231102305
/content/journals/cmm/10.2174/0115665240343441241231102305
/content/journals/cmm/10.2174/0115665240343441241231102305
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): bathwater PUVA; FOSL1; gene expression; HaCaT; Psoriasis; S100A7; shRNA

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