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Article: miR-200c Prevents TGF-β1-Induced Epithelial-to-Mesenchymal Transition and Fibrogenesis in Mesothelial Cells by Targeting ZEB2 and Notch1

TitlemiR-200c Prevents TGF-β1-Induced Epithelial-to-Mesenchymal Transition and Fibrogenesis in Mesothelial Cells by Targeting ZEB2 and Notch1
Authors
KeywordsMesothelial cells
miR-200c
TGF-β1
EMT
Fibrosis
Issue Date2019
PublisherElsevier (Cell Press): OAJ. The Journal's web site is located at http://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content
Citation
Molecular Therapy - Nucleic Acids, 2019, v. 17, p. 78-91 How to Cite?
AbstractPeritoneal fibrosis and loss of transport function is a common complication contributing to adverse outcomes in patients on long-term peritoneal dialysis (PD). Epithelial-to-mesenchymal transition (EMT) in mesothelial cells is a salient feature, but its triggering mechanisms remain obscure. Dysregulation of microRNA (miR) expression is implicated in EMT and tissue fibrosis. We investigated the role of miR-200c in EMT and fibrogenesis in a murine PD model and in cultured peritoneal mesothelial cells. PD-fluid-treated mice showed peritoneal miR-200c expression reduced by 76.2% compared with PBS-treated mice, and this was accompanied by increased peritoneal α-smooth muscle actin, fibronectin, and collagen expression. PD fluid and TGF-β1 both reduced miR-200c expression in cultured mesothelial cells, accompanied by downregulation of E-cadherin and decorin, and induction of fibronectin, collagen I and III, and transcription factors related to EMT. Decorin prevented the suppression of miR-200c by TGF-β1. Lentivirus-mediated miR-200c overexpression prevented the induction of fibronectin, collagen I, and collagen III by TGF-β1, independent of decorin, and partially prevented E-cadherin suppression by TGF-β1. Target genes of miR-200c were identified as ZEB2 and Notch1. Our data demonstrate that miR-200c regulates EMT and fibrogenesis in mesothelial cells, and loss of peritoneal miR-200c contributes to PD-associated peritoneal fibrosis.
Persistent Identifierhttp://hdl.handle.net/10722/272563
ISSN
2017 Impact Factor: 5.66
2015 SCImago Journal Rankings: 2.320
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorChu, JYS-
dc.contributor.authorChau, MKM-
dc.contributor.authorChan, CCY-
dc.contributor.authorTai, ACP-
dc.contributor.authorCheung, KF-
dc.contributor.authorChan, TM-
dc.contributor.authorYung, S-
dc.date.accessioned2019-07-23T04:08:04Z-
dc.date.available2019-07-23T04:08:04Z-
dc.date.issued2019-
dc.identifier.citationMolecular Therapy - Nucleic Acids, 2019, v. 17, p. 78-91-
dc.identifier.issn2162-2531-
dc.identifier.urihttp://hdl.handle.net/10722/272563-
dc.description.abstractPeritoneal fibrosis and loss of transport function is a common complication contributing to adverse outcomes in patients on long-term peritoneal dialysis (PD). Epithelial-to-mesenchymal transition (EMT) in mesothelial cells is a salient feature, but its triggering mechanisms remain obscure. Dysregulation of microRNA (miR) expression is implicated in EMT and tissue fibrosis. We investigated the role of miR-200c in EMT and fibrogenesis in a murine PD model and in cultured peritoneal mesothelial cells. PD-fluid-treated mice showed peritoneal miR-200c expression reduced by 76.2% compared with PBS-treated mice, and this was accompanied by increased peritoneal α-smooth muscle actin, fibronectin, and collagen expression. PD fluid and TGF-β1 both reduced miR-200c expression in cultured mesothelial cells, accompanied by downregulation of E-cadherin and decorin, and induction of fibronectin, collagen I and III, and transcription factors related to EMT. Decorin prevented the suppression of miR-200c by TGF-β1. Lentivirus-mediated miR-200c overexpression prevented the induction of fibronectin, collagen I, and collagen III by TGF-β1, independent of decorin, and partially prevented E-cadherin suppression by TGF-β1. Target genes of miR-200c were identified as ZEB2 and Notch1. Our data demonstrate that miR-200c regulates EMT and fibrogenesis in mesothelial cells, and loss of peritoneal miR-200c contributes to PD-associated peritoneal fibrosis.-
dc.languageeng-
dc.publisherElsevier (Cell Press): OAJ. The Journal's web site is located at http://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content-
dc.relation.ispartofMolecular Therapy - Nucleic Acids-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectMesothelial cells-
dc.subjectmiR-200c-
dc.subjectTGF-β1-
dc.subjectEMT-
dc.subjectFibrosis-
dc.titlemiR-200c Prevents TGF-β1-Induced Epithelial-to-Mesenchymal Transition and Fibrogenesis in Mesothelial Cells by Targeting ZEB2 and Notch1-
dc.typeArticle-
dc.identifier.emailChu, JYS: jyschu@hku.hk-
dc.identifier.emailChan, CCY: calebccy@hku.hk-
dc.identifier.emailTai, ACP: cpandrew@hku.hk-
dc.identifier.emailChan, TM: dtmchan@hku.hk-
dc.identifier.emailYung, S: ssyyung@hku.hk-
dc.identifier.authorityChu, JYS=rp00684-
dc.identifier.authorityChan, TM=rp00394-
dc.identifier.authorityYung, S=rp00455-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.omtn.2019.05.008-
dc.identifier.pmid31226520-
dc.identifier.pmcidPMC6586597-
dc.identifier.scopuseid_2-s2.0-85067275129-
dc.identifier.hkuros299783-
dc.identifier.volume17-
dc.identifier.spage78-
dc.identifier.epage91-
dc.publisher.placeUnited Kingdom-

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