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2000
Volume 17, Issue 1
  • ISSN: 1874-4672
  • E-ISSN: 1874-4702

Abstract

Background

Asthma is a chronic airway disease characterized by Airway Remodeling (AR) and persistent inflammation, with Epithelial-Mesenchymal Transition (EMT) playing a crucial role in fibrosis and smooth muscle proliferation. The Transforming Growth Factor-Beta1 (TGFβ1)/Smad pathway is a key driver of EMT in asthma. Current treatments do not effectively prevent AR progression. Traditional Chinese Medicine, particularly the Xuanfei Pingchuan (XFPC) prescription, has shown potential in managing asthma, but its role in EMT regulation remains unclear.

Methods

This study explored the role of “phlegm and stasis” in airway remodeling (AR) in asthma from the perspective of EMT and investigated the effects and underlying mechanisms of XFPC prescription on EMT in AR. , human bronchial epithelial (16HBE) cells were induced into EMT with TGFβ1 and treated with XFPC drug-containing serum, with EMT marker expression analyzed RT-qPCR and Western blot. , an ovalbumin (OVA)-induced asthma model in Sprague Dawley rats was used to evaluate the effects of different XFPC doses through histopathology, immunofluorescence, and molecular analyses. Additionally, Smurf2 cDNA transfection was conducted to assess the role of Smurf2 in EMT regulation.

Results

The results confirmed that XFPC prescription suppressed the pathway of transforming-growth factor-beta1 (TGFβ1)-Smad by reducing Smad ubiquitination regulator 2 (Smurf2), Smad2, Smad3, TGFβ1 receptor (TβRI), N-cadherin, α-SMA, and Vimentin in terms of expressions at messenger ribonucleic acid (mRNA) and protein levels. However, XFPC prescription up-regulated expressions of SnoN and E-cadherin at protein and mRNA levels to inhibit EMT. The result also confirmed that XFPC prescription decreased the ubiquitination of Smad7.

Conclusion

XFPC prescription could suppress AR in TGFβ1 induced 16HBE cells and OVA-sensitized animal models through TGFβ1/Smad pathway.

© 2024 The Author(s). Published by Bentham Science Publishers. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2024-01-01
2025-09-05
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References

  1. LiC.H. TsaiM.L. ChiouH.Y.C. LinY.C. LiaoW.T. HungC.H. Role of macrophages in air pollution exposure related asthma.Int. J. Mol. Sci.202223201233710.3390/ijms23201233736293195
    [Google Scholar]
  2. PniewskaE. SokolowskaM. Kupryś-LipińskaI. KacprzakD. KunaP. PawliczakR. Exacerbating factors induce different gene expression profiles in peripheral blood mononuclear cells from asthmatics, patients with chronic obstructive pulmonary disease and healthy subjects.Int. Arch. Allergy Immunol.2014165422924310.1159/00037006725634111
    [Google Scholar]
  3. WrightD.B. MeursH. DekkersB.G.J. Integrins: Therapeutic targets in airway hyperresponsiveness and remodelling?Trends Pharmacol. Sci.2014351156757410.1016/j.tips.2014.09.00625441775
    [Google Scholar]
  4. KhalfaouiL. PabelickC.M. Airway smooth muscle in contractility and remodeling of asthma: Potential drug target mechanisms.Expert Opin. Ther. Targets2023271192910.1080/14728222.2023.217753336744401
    [Google Scholar]
  5. GoldsteinB.D. LauerM.E. CaplanA.I. BonfieldT.L. Chronic asthma and Mesenchymal stem cells: Hyaluronan and airway remodeling.J. Inflamm.20171411810.1186/s12950‑017‑0165‑428860944
    [Google Scholar]
  6. NoguchiS. YamauchiY. TakizawaH. Novel therapeutic strategies for fibrotic lung disease: A review with a focus on epithelial-mesenchymal transition.Recent Pat. Inflamm. Allergy Drug Discov.20148191810.2174/1872213X0766613122913145124383438
    [Google Scholar]
  7. ThevenotP.T. SaraviaJ. JinN. GiaimoJ.D. ChustzR.E. MahneS. KelleyM.A. HebertV.Y. DellingerB. DugasT.R. DeMayoF.J. CormierS.A. Radical-containing ultrafine particulate matter initiates epithelial-to-mesenchymal transitions in airway epithelial cells.Am. J. Respir. Cell Mol. Biol.201348218819710.1165/rcmb.2012‑0052OC23087054
    [Google Scholar]
  8. YaoL. WangS. WeiP. BaoK. YuanW. WangX. ZhengJ. HongM. Huangqi–Fangfeng protects against allergic airway remodeling through inhibiting epithelial–mesenchymal transition process in mice via regulating epithelial derived TGF-β1.Phytomedicine20196415307610.1016/j.phymed.2019.15307631473579
    [Google Scholar]
  9. LiuP. LiS. TangL. Nerve growth factor: A potential therapeutic target for lung diseases.Int. J. Mol. Sci.20212217911210.3390/ijms2217911234502019
    [Google Scholar]
  10. SunZ. JiN. MaQ. ZhuR. ChenZ. WangZ. QianY. WuC. HuF. HuangM. ZhangM. Epithelial-mesenchymal transition in asthma airway remodeling is regulated by the IL-33/CD146 axis.Front. Immunol.202011159810.3389/fimmu.2020.0159832793232
    [Google Scholar]
  11. StalinJ. NolletM. Dignat-GeorgeF. BardinN. Blot-ChabaudM. Therapeutic and diagnostic antibodies to CD146: Thirty years of research on its potential for detection and treatment of tumors.Antibodies2017641710.3390/antib604001731548532
    [Google Scholar]
  12. LiuY.B. TanX.H. YangH.H. YangJ.T. ZhangC.Y. JinL. YangN.S.Y. GuanC.X. ZhouY. LiuS.K. XiongJ.B. Wnt5a-mediated autophagy contributes to the epithelial-mesenchymal transition of human bronchial epithelial cells during asthma.Mol. Med.20243019310.1186/s10020‑024‑00862‑338898476
    [Google Scholar]
  13. FengK. MengP. ZouX. ZhangM. LiH. YangH. LiH. ZhangT. IL-37 protects against airway remodeling by reversing bronchial epithelial–mesenchymal transition via IL-24 signaling pathway in chronic asthma.Respir. Res.202223124410.1186/s12931‑022‑02167‑736100847
    [Google Scholar]
  14. YoshieS. MuronoS. HazamaA. Approach for elucidating the molecular mechanism of epithelial to mesenchymal transition in fibrosis of asthmatic airway remodeling focusing on Cl− channels.Int. J. Mol. Sci.202325128910.3390/ijms2501028938203460
    [Google Scholar]
  15. KobayashiK. KoyamaK. SuzukawaM. IgarashiS. HebisawaA. NagaseT. Epithelial-mesenchymal transition promotes reactivity of human lung adenocarcinoma A549 cells to CpG ODN.Allergol. Int.201665S45S5210.1016/j.alit.2016.06.010
    [Google Scholar]
  16. DesaiP. YangJ. TianB. SunH. KalitaM. JuH. Paulucci-HolthauzenA. ZhaoY. BrasierA.R. SadygovR.G. Mixed-effects model of epithelial–mesenchymal transition reveals rewiring of signaling networks.Cell. Signal.20152771413142510.1016/j.cellsig.2015.03.02425862520
    [Google Scholar]
  17. YouJ. WangJ. XieL. ZhuC. XiongJ. D-4F, an apolipoprotein A-I mimetic, inhibits TGF-β1 induced epithelial-mesenchymal transition in human alveolar epithelial cell.Exp. Toxicol. Pathol.201668953354110.1016/j.etp.2016.07.00527495007
    [Google Scholar]
  18. WeiY. ZhangZ. WangF. ZhouS. Assessment of tumor growth factor-β1 neutralizing antibody in the treatment of allergic rhinitis and asthma.Exp. Ther. Med.201815164965629399067
    [Google Scholar]
  19. YangZ.C. QuZ.H. YiM.J. ShanY.C. RanN. XuL. LiuX.J. MiR‐448‐5p inhibits TGF‐β1‐induced epithelial‐mesenchymal transition and pulmonary fibrosis by targeting Six1 in asthma.J. Cell. Physiol.201923468804881410.1002/jcp.2754030362537
    [Google Scholar]
  20. ChuS. ZhangX. SunY. YuY. LiangY. JiangM. HuangJ. MaL. Atrial natriuretic peptide: A novel mediator for TGF-β1-induced epithelial-mesenchymal transition in 16HBE-14o and A549 cells.Peptides2017901910.1016/j.peptides.2017.02.00228229930
    [Google Scholar]
  21. DerynckR. MuthusamyB.P. SaeteurnK.Y. Signaling pathway cooperation in TGF-β-induced epithelial–mesenchymal transition.Curr. Opin. Cell Biol.201431566610.1016/j.ceb.2014.09.00125240174
    [Google Scholar]
  22. SistoM. LorussoL. IngravalloG. RibattiD. LisiS. TGFβ1-Smad canonical and -Erk noncanonical pathways participate in interleukin-17-induced epithelial–mesenchymal transition in Sjögren’s syndrome.Lab. Invest.2020100682483610.1038/s41374‑020‑0373‑z31925325
    [Google Scholar]
  23. HataA. ChenY.G. TGF-β signaling from receptors to smads.Cold Spring Harb. Perspect. Biol.201689a02206110.1101/cshperspect.a02206127449815
    [Google Scholar]
  24. YangY. ZhangN. LanF. Van CrombruggenK. FangL. HuG. HongS. BachertC. Transforming growth factor‐beta 1 pathways in inflammatory airway diseases.Allergy201469669970710.1111/all.1240324750111
    [Google Scholar]
  25. Rout-PittN. FarrowN. ParsonsD. DonnelleyM. Epithelial mesenchymal transition (EMT): A universal process in lung diseases with implications for cystic fibrosis pathophysiology.Respir. Res.201819113610.1186/s12931‑018‑0834‑830021582
    [Google Scholar]
  26. JosephC. TatlerA. Pathobiology of airway remodeling in asthma: The emerging role of integrins.J. Asthma Allergy20221559561010.2147/JAA.S26722235592385
    [Google Scholar]
  27. Tonggang Zhu Xue Xiao Yufu Dong YuanC. Neferine alleviates ovalbumin-induced asthma via MAPK signaling pathways in mice.Allergol. Immunopathol.202351313514210.15586/aei.v51i3.84037169571
    [Google Scholar]
  28. XueX. MengL. CaiH. SunY. ZhangY. LiH. KangY. ZhouB. ShangF. GuanW. ZhangL. ChenX. ZhangL. Xuanfei pingchuan capsules ameliorate autophagy in human bronchial epithelial cells by inhibiting p38 phosphorylation.Front. Pharmacol.20211274823410.3389/fphar.2021.74823434925010
    [Google Scholar]
  29. JiangW. QiJ. LiX. ChenG. ZhouD. XiaoW. LiN. Post-infectious cough of different syndromes treated by traditional Chinese medicines: A review.Chin. Herb. Med.202214449451010.1016/j.chmed.2022.09.00236405059
    [Google Scholar]
  30. ZhangY. XueX. MengL. LiD. QiaoW. WangJ. XieD. Roles of autophagy-related genes in the therapeutic effects of Xuanfei Pingchuan capsules on chronic obstructive pulmonary disease based on transcriptome sequencing analysis.Front. Pharmacol.202314112388210.3389/fphar.2023.112388237274101
    [Google Scholar]
  31. LiC. DaiJ. DongG. MaQ. LiZ. ZhangH. YanF. ZhangJ. WangB. ShiH. ZhuY. YaoX. SiC. XiongH. Interleukin‐16 aggravates ovalbumin‐induced allergic inflammation by enhancing Th2 and Th17 cytokine production in a mouse model.Immunology2019157325726710.1111/imm.1306831120548
    [Google Scholar]
  32. HeQ. PanX. YinY. XuA. YiX. WuY. LiX. Clonorchis sinensis granulin promotes malignant transformation of human intrahepatic biliary epithelial cells through interaction with M2 macrophages via regulation of STAT3 phosphorylation and the MEK/ERK pathway.Parasit. Vectors202316113910.1186/s13071‑023‑05765‑637095578
    [Google Scholar]
  33. RaoX. HuangX. ZhouZ. LinX. An improvement of the 2ˆ(-delta delta CT) method for quantitative real-time polymerase chain reaction data analysis.Biostat. Bioinforma. Biomath.201333718525558171
    [Google Scholar]
  34. XuL. XiangX. JiX. WangW. LuoM. LuoS. LiK. GongS. LiuS. MaL. ChenP. LiJ. Effects and mechanism of dehydroepiandrosterone on epithelial–mesenchymal transition in bronchial epithelial cells.Exp. Lung Res.201440521122110.3109/01902148.2013.87996624784499
    [Google Scholar]
  35. DongZ. TaiW. LeiW. WangY. LiZ. ZhangT. IL-27 inhibits the TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells.BMC Cell Biol.2016171710.1186/s12860‑016‑0084‑x26932661
    [Google Scholar]
  36. ZhangZ. LiuC. ChenB. TangW. LiuZ. CaoW. LiX. Smad7 down-regulation via ubiquitin degradation mediated by Smurf2 in fibroblasts of hypertrophic scars in burned patients.Burns20214761333134110.1016/j.burns.2020.12.01733436154
    [Google Scholar]
  37. XuF. LiuC. ZhouD. ZhangL. TGF-β/SMAD pathway and its regulation in hepatic fibrosis.J. Histochem. Cytochem.201664315716710.1369/002215541562768126747705
    [Google Scholar]
  38. XiaoX. HuangC. ZhaoC. GouX. SenavirathnaL.K. HinsdaleM. LloydP. LiuL. Regulation of myofibroblast differentiation by miR-424 during epithelial-to-mesenchymal transition.Arch. Biochem. Biophys.2015566495710.1016/j.abb.2014.12.00725524739
    [Google Scholar]
  39. MaL. LiH. ZhangS. XiongX. ChenK. JiangP. JiangK. DengG. Emodin ameliorates renal fibrosis in rats via TGF-β1/Smad signaling pathway and function study of Smurf 2.Int. Urol. Nephrol.201850237338210.1007/s11255‑017‑1757‑x29230704
    [Google Scholar]
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