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Article: microRNA-29b prevents liver fibrosis by attenuating hepatic stellate cell activation and inducing apoptosis through targeting PI3K/AKT pathway

TitlemicroRNA-29b prevents liver fibrosis by attenuating hepatic stellate cell activation and inducing apoptosis through targeting PI3K/AKT pathway
Authors
Issue Date2015
PublisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html
Citation
Oncotarget, 2015, v. 6 n. 9, p. 7325-7338 How to Cite?
AbstractmicroRNA-29b (miR-29b) is known to be associated with TGF-β-mediated fibrosis, but the mechanistic action of miR-29b in liver fibrosis remains unclear and is warranted for investigation. We found that miR-29b was significantly downregulated in human and mice fibrotic liver tissues and in primary activated HSCs. miR-29b downregulation was directly mediated by Smad3 through binding to the promoter of miR-29b in hepatic stellate cell (HSC) line LX1, whilst miR-29b could in turn suppress Smad3 expression. miR-29b transduction in the liver of mice prevented CCl4 induced-fibrogenesis, concomitant with decreased expression of α-SMA, collagen I and TIMP-1. Ectopic expression of miR-29b in activated HSCs (LX-1, HSC-T6) inhibited cell viability and colony formation, and caused cell cycle arrest in G1 phase by downregulating cyclin D1 and p21cip1. Further, miR-29b induced apoptosis in HSCs mediated by caspase-9 and PARP. miR-29b inhibited its downstream effectors of PIK3R1 and AKT3 through direct targeting their 3'UTR regions. Moreover, knockdown of PIK3R1 or AKT3 suppressed α-SMA and collagen I and induced apoptosis in both HSCs and in mice. In conclusion, miR-29b prevents liver fibrogenesis by inhibiting HSC activation and inducing HSC apoptosis through inhibiting PI3K/AKT pathway. These results provide novel mechanistic insights for the anti-fibrotic effect of miR-29b.
Persistent Identifierhttp://hdl.handle.net/10722/207324
ISSN
2015 Impact Factor: 5.008
2015 SCImago Journal Rankings: 2.294
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorWang, J-
dc.contributor.authorChu, ESH-
dc.contributor.authorChen, HY-
dc.contributor.authorMan, K-
dc.contributor.authorGo, MYY-
dc.contributor.authorHuang, XR-
dc.contributor.authorLan, HY-
dc.contributor.authorSung, JJY-
dc.contributor.authorYu, J-
dc.date.accessioned2014-12-19T10:20:57Z-
dc.date.available2014-12-19T10:20:57Z-
dc.date.issued2015-
dc.identifier.citationOncotarget, 2015, v. 6 n. 9, p. 7325-7338-
dc.identifier.issn1949-2553-
dc.identifier.urihttp://hdl.handle.net/10722/207324-
dc.description.abstractmicroRNA-29b (miR-29b) is known to be associated with TGF-β-mediated fibrosis, but the mechanistic action of miR-29b in liver fibrosis remains unclear and is warranted for investigation. We found that miR-29b was significantly downregulated in human and mice fibrotic liver tissues and in primary activated HSCs. miR-29b downregulation was directly mediated by Smad3 through binding to the promoter of miR-29b in hepatic stellate cell (HSC) line LX1, whilst miR-29b could in turn suppress Smad3 expression. miR-29b transduction in the liver of mice prevented CCl4 induced-fibrogenesis, concomitant with decreased expression of α-SMA, collagen I and TIMP-1. Ectopic expression of miR-29b in activated HSCs (LX-1, HSC-T6) inhibited cell viability and colony formation, and caused cell cycle arrest in G1 phase by downregulating cyclin D1 and p21cip1. Further, miR-29b induced apoptosis in HSCs mediated by caspase-9 and PARP. miR-29b inhibited its downstream effectors of PIK3R1 and AKT3 through direct targeting their 3'UTR regions. Moreover, knockdown of PIK3R1 or AKT3 suppressed α-SMA and collagen I and induced apoptosis in both HSCs and in mice. In conclusion, miR-29b prevents liver fibrogenesis by inhibiting HSC activation and inducing HSC apoptosis through inhibiting PI3K/AKT pathway. These results provide novel mechanistic insights for the anti-fibrotic effect of miR-29b.-
dc.languageeng-
dc.publisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html-
dc.relation.ispartofOncotarget-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titlemicroRNA-29b prevents liver fibrosis by attenuating hepatic stellate cell activation and inducing apoptosis through targeting PI3K/AKT pathway-
dc.typeArticle-
dc.identifier.emailChen, HY: haiyong@hku.hk-
dc.identifier.emailMan, K: kwanman@hku.hk-
dc.identifier.authorityChen, HY=rp01923-
dc.identifier.authorityMan, K=rp00417-
dc.description.naturepublished_or_final_version-
dc.identifier.pmid25356754-
dc.identifier.pmcidPMC4466688-
dc.identifier.hkuros241987-
dc.identifier.hkuros247561-
dc.identifier.volume6-
dc.identifier.issue9-
dc.identifier.spage7325-
dc.identifier.epage7338-
dc.publisher.placeUnited States-

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