microRNA-29b prevents liver fibrosis by attenuating hepatic stellate cell activation and inducing apoptosis through targeting PI3K/AKT pathway
Identifieur interne : 000C43 ( Main/Merge ); précédent : 000C42; suivant : 000C44microRNA-29b prevents liver fibrosis by attenuating hepatic stellate cell activation and inducing apoptosis through targeting PI3K/AKT pathway
Auteurs : Jia Wang [Hong Kong, République populaire de Chine] ; Eagle S. H. Chu [Hong Kong, République populaire de Chine] ; Hai-Yong Chen [Hong Kong] ; Kwan Man [Hong Kong] ; Minnie Y. Y. Go [Hong Kong] ; Xiao Ru Huang [Hong Kong] ; Hui Yao Lan [Hong Kong] ; Joseph J. Y. Sung [Hong Kong, République populaire de Chine] ; Jun Yu [Hong Kong, République populaire de Chine]Source :
- Oncotarget [ 1949-2553 ] ; 2014.
Abstract
microRNA-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.
Url:
PubMed: 25356754
PubMed Central: 4466688
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000259
- to stream Pmc, to step Curation: 000259
- to stream Pmc, to step Checkpoint: 000802
- to stream Ncbi, to step Merge: 003412
- to stream Ncbi, to step Curation: 003412
- to stream Ncbi, to step Checkpoint: 003412
Links to Exploration step
PMC:4466688Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">microRNA-29b prevents liver fibrosis by attenuating hepatic stellate cell activation and inducing apoptosis through targeting PI3K/AKT pathway</title>
<author><name sortKey="Wang, Jia" sort="Wang, Jia" uniqKey="Wang J" first="Jia" last="Wang">Jia Wang</name>
<affiliation wicri:level="4"><nlm:aff id="A1"> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong</wicri:regionArea>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
<orgName type="university">Université chinoise de Hong Kong</orgName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A2"> Gastrointestinal Cancer Biology & Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea> Gastrointestinal Cancer Biology & Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen</wicri:regionArea>
<placeName><settlement type="city">Shenzhen</settlement>
<region type="province">Guangdong</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chu, Eagle S H" sort="Chu, Eagle S H" uniqKey="Chu E" first="Eagle S. H." last="Chu">Eagle S. H. Chu</name>
<affiliation wicri:level="4"><nlm:aff id="A1"> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong</wicri:regionArea>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
<orgName type="university">Université chinoise de Hong Kong</orgName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A2"> Gastrointestinal Cancer Biology & Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea> Gastrointestinal Cancer Biology & Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen</wicri:regionArea>
<placeName><settlement type="city">Shenzhen</settlement>
<region type="province">Guangdong</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chen, Hai Yong" sort="Chen, Hai Yong" uniqKey="Chen H" first="Hai-Yong" last="Chen">Hai-Yong Chen</name>
<affiliation wicri:level="4"><nlm:aff id="A1"> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong</wicri:regionArea>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
<orgName type="university">Université chinoise de Hong Kong</orgName>
</affiliation>
</author>
<author><name sortKey="Man, Kwan" sort="Man, Kwan" uniqKey="Man K" first="Kwan" last="Man">Kwan Man</name>
<affiliation wicri:level="1"><nlm:aff id="A3"> Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea> Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong</wicri:regionArea>
<wicri:noRegion>The University of Hong Kong</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Go, Minnie Y Y" sort="Go, Minnie Y Y" uniqKey="Go M" first="Minnie Y. Y." last="Go">Minnie Y. Y. Go</name>
<affiliation wicri:level="4"><nlm:aff id="A1"> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong</wicri:regionArea>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
<orgName type="university">Université chinoise de Hong Kong</orgName>
</affiliation>
</author>
<author><name sortKey="Huang, Xiao Ru" sort="Huang, Xiao Ru" uniqKey="Huang X" first="Xiao Ru" last="Huang">Xiao Ru Huang</name>
<affiliation wicri:level="4"><nlm:aff id="A1"> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong</wicri:regionArea>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
<orgName type="university">Université chinoise de Hong Kong</orgName>
</affiliation>
</author>
<author><name sortKey="Lan, Hui Yao" sort="Lan, Hui Yao" uniqKey="Lan H" first="Hui Yao" last="Lan">Hui Yao Lan</name>
<affiliation wicri:level="4"><nlm:aff id="A1"> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong</wicri:regionArea>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
<orgName type="university">Université chinoise de Hong Kong</orgName>
</affiliation>
</author>
<author><name sortKey="Sung, Joseph J Y" sort="Sung, Joseph J Y" uniqKey="Sung J" first="Joseph J. Y." last="Sung">Joseph J. Y. Sung</name>
<affiliation wicri:level="4"><nlm:aff id="A1"> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong</wicri:regionArea>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
<orgName type="university">Université chinoise de Hong Kong</orgName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A2"> Gastrointestinal Cancer Biology & Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea> Gastrointestinal Cancer Biology & Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen</wicri:regionArea>
<placeName><settlement type="city">Shenzhen</settlement>
<region type="province">Guangdong</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yu, Jun" sort="Yu, Jun" uniqKey="Yu J" first="Jun" last="Yu">Jun Yu</name>
<affiliation wicri:level="4"><nlm:aff id="A1"> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong</wicri:regionArea>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
<orgName type="university">Université chinoise de Hong Kong</orgName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A2"> Gastrointestinal Cancer Biology & Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea> Gastrointestinal Cancer Biology & Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen</wicri:regionArea>
<placeName><settlement type="city">Shenzhen</settlement>
<region type="province">Guangdong</region>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">25356754</idno>
<idno type="pmc">4466688</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466688</idno>
<idno type="RBID">PMC:4466688</idno>
<date when="2014">2014</date>
<idno type="wicri:Area/Pmc/Corpus">000259</idno>
<idno type="wicri:Area/Pmc/Curation">000259</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000802</idno>
<idno type="wicri:Area/Ncbi/Merge">003412</idno>
<idno type="wicri:Area/Ncbi/Curation">003412</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">003412</idno>
<idno type="wicri:Area/Main/Merge">000C43</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">microRNA-29b prevents liver fibrosis by attenuating hepatic stellate cell activation and inducing apoptosis through targeting PI3K/AKT pathway</title>
<author><name sortKey="Wang, Jia" sort="Wang, Jia" uniqKey="Wang J" first="Jia" last="Wang">Jia Wang</name>
<affiliation wicri:level="4"><nlm:aff id="A1"> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong</wicri:regionArea>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
<orgName type="university">Université chinoise de Hong Kong</orgName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A2"> Gastrointestinal Cancer Biology & Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea> Gastrointestinal Cancer Biology & Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen</wicri:regionArea>
<placeName><settlement type="city">Shenzhen</settlement>
<region type="province">Guangdong</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chu, Eagle S H" sort="Chu, Eagle S H" uniqKey="Chu E" first="Eagle S. H." last="Chu">Eagle S. H. Chu</name>
<affiliation wicri:level="4"><nlm:aff id="A1"> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong</wicri:regionArea>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
<orgName type="university">Université chinoise de Hong Kong</orgName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A2"> Gastrointestinal Cancer Biology & Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea> Gastrointestinal Cancer Biology & Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen</wicri:regionArea>
<placeName><settlement type="city">Shenzhen</settlement>
<region type="province">Guangdong</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chen, Hai Yong" sort="Chen, Hai Yong" uniqKey="Chen H" first="Hai-Yong" last="Chen">Hai-Yong Chen</name>
<affiliation wicri:level="4"><nlm:aff id="A1"> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong</wicri:regionArea>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
<orgName type="university">Université chinoise de Hong Kong</orgName>
</affiliation>
</author>
<author><name sortKey="Man, Kwan" sort="Man, Kwan" uniqKey="Man K" first="Kwan" last="Man">Kwan Man</name>
<affiliation wicri:level="1"><nlm:aff id="A3"> Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea> Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong</wicri:regionArea>
<wicri:noRegion>The University of Hong Kong</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Go, Minnie Y Y" sort="Go, Minnie Y Y" uniqKey="Go M" first="Minnie Y. Y." last="Go">Minnie Y. Y. Go</name>
<affiliation wicri:level="4"><nlm:aff id="A1"> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong</wicri:regionArea>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
<orgName type="university">Université chinoise de Hong Kong</orgName>
</affiliation>
</author>
<author><name sortKey="Huang, Xiao Ru" sort="Huang, Xiao Ru" uniqKey="Huang X" first="Xiao Ru" last="Huang">Xiao Ru Huang</name>
<affiliation wicri:level="4"><nlm:aff id="A1"> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong</wicri:regionArea>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
<orgName type="university">Université chinoise de Hong Kong</orgName>
</affiliation>
</author>
<author><name sortKey="Lan, Hui Yao" sort="Lan, Hui Yao" uniqKey="Lan H" first="Hui Yao" last="Lan">Hui Yao Lan</name>
<affiliation wicri:level="4"><nlm:aff id="A1"> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong</wicri:regionArea>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
<orgName type="university">Université chinoise de Hong Kong</orgName>
</affiliation>
</author>
<author><name sortKey="Sung, Joseph J Y" sort="Sung, Joseph J Y" uniqKey="Sung J" first="Joseph J. Y." last="Sung">Joseph J. Y. Sung</name>
<affiliation wicri:level="4"><nlm:aff id="A1"> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong</wicri:regionArea>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
<orgName type="university">Université chinoise de Hong Kong</orgName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A2"> Gastrointestinal Cancer Biology & Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea> Gastrointestinal Cancer Biology & Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen</wicri:regionArea>
<placeName><settlement type="city">Shenzhen</settlement>
<region type="province">Guangdong</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yu, Jun" sort="Yu, Jun" uniqKey="Yu J" first="Jun" last="Yu">Jun Yu</name>
<affiliation wicri:level="4"><nlm:aff id="A1"> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea> Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong</wicri:regionArea>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
<orgName type="university">Université chinoise de Hong Kong</orgName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A2"> Gastrointestinal Cancer Biology & Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea> Gastrointestinal Cancer Biology & Therapeutics Laboratory, CUHK-Shenzhen Research Institute, Shenzhen</wicri:regionArea>
<placeName><settlement type="city">Shenzhen</settlement>
<region type="province">Guangdong</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Oncotarget</title>
<idno type="eISSN">1949-2553</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>microRNA-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 CCl<sub>4</sub>
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 p21<sup>cip1</sup>
. 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.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Popov, Y" uniqKey="Popov Y">Y Popov</name>
</author>
<author><name sortKey="Schuppan, D" uniqKey="Schuppan D">D Schuppan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Albanis, E" uniqKey="Albanis E">E Albanis</name>
</author>
<author><name sortKey="Friedman, Sl" uniqKey="Friedman S">SL Friedman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Moreira, Rk" uniqKey="Moreira R">RK Moreira</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Reeves, Hl" uniqKey="Reeves H">HL Reeves</name>
</author>
<author><name sortKey="Friedman, Sl" uniqKey="Friedman S">SL Friedman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dooley, S" uniqKey="Dooley S">S Dooley</name>
</author>
<author><name sortKey="Delvoux, B" uniqKey="Delvoux B">B Delvoux</name>
</author>
<author><name sortKey="Lahme, B" uniqKey="Lahme B">B Lahme</name>
</author>
<author><name sortKey="Mangasser Stephan, K" uniqKey="Mangasser Stephan K">K Mangasser-Stephan</name>
</author>
<author><name sortKey="Gressner, Am" uniqKey="Gressner A">AM Gressner</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Galli, A" uniqKey="Galli A">A Galli</name>
</author>
<author><name sortKey="Crabb, Dw" uniqKey="Crabb D">DW Crabb</name>
</author>
<author><name sortKey="Ceni, E" uniqKey="Ceni E">E Ceni</name>
</author>
<author><name sortKey="Salzano, R" uniqKey="Salzano R">R Salzano</name>
</author>
<author><name sortKey="Mello, T" uniqKey="Mello T">T Mello</name>
</author>
<author><name sortKey="Svegliati Baroni, G" uniqKey="Svegliati Baroni G">G Svegliati-Baroni</name>
</author>
<author><name sortKey="Ridolfi, F" uniqKey="Ridolfi F">F Ridolfi</name>
</author>
<author><name sortKey="Trozzi, L" uniqKey="Trozzi L">L Trozzi</name>
</author>
<author><name sortKey="Surrenti, C" uniqKey="Surrenti C">C Surrenti</name>
</author>
<author><name sortKey="Casini, A" uniqKey="Casini A">A Casini</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Iredale, Jp" uniqKey="Iredale J">JP Iredale</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Benyon, Rc" uniqKey="Benyon R">RC Benyon</name>
</author>
<author><name sortKey="Arthur, Mj" uniqKey="Arthur M">MJ Arthur</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Friedman, Sl" uniqKey="Friedman S">SL Friedman</name>
</author>
<author><name sortKey="Bansal, Mb" uniqKey="Bansal M">MB Bansal</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bartel, Dp" uniqKey="Bartel D">DP Bartel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ura, S" uniqKey="Ura S">S Ura</name>
</author>
<author><name sortKey="Honda, M" uniqKey="Honda M">M Honda</name>
</author>
<author><name sortKey="Yamashita, T" uniqKey="Yamashita T">T Yamashita</name>
</author>
<author><name sortKey="Ueda, T" uniqKey="Ueda T">T Ueda</name>
</author>
<author><name sortKey="Takatori, H" uniqKey="Takatori H">H Takatori</name>
</author>
<author><name sortKey="Nishino, R" uniqKey="Nishino R">R Nishino</name>
</author>
<author><name sortKey="Sunakozaka, H" uniqKey="Sunakozaka H">H Sunakozaka</name>
</author>
<author><name sortKey="Sakai, Y" uniqKey="Sakai Y">Y Sakai</name>
</author>
<author><name sortKey="Horimoto, K" uniqKey="Horimoto K">K Horimoto</name>
</author>
<author><name sortKey="Kaneko, S" uniqKey="Kaneko S">S Kaneko</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jin, X" uniqKey="Jin X">X Jin</name>
</author>
<author><name sortKey="Ye, Yf" uniqKey="Ye Y">YF Ye</name>
</author>
<author><name sortKey="Chen, Sh" uniqKey="Chen S">SH Chen</name>
</author>
<author><name sortKey="Yu, Ch" uniqKey="Yu C">CH Yu</name>
</author>
<author><name sortKey="Liu, J" uniqKey="Liu J">J Liu</name>
</author>
<author><name sortKey="Li, Ym" uniqKey="Li Y">YM Li</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Murakami, Y" uniqKey="Murakami Y">Y Murakami</name>
</author>
<author><name sortKey="Yasuda, T" uniqKey="Yasuda T">T Yasuda</name>
</author>
<author><name sortKey="Saigo, K" uniqKey="Saigo K">K Saigo</name>
</author>
<author><name sortKey="Urashima, T" uniqKey="Urashima T">T Urashima</name>
</author>
<author><name sortKey="Toyoda, H" uniqKey="Toyoda H">H Toyoda</name>
</author>
<author><name sortKey="Okanoue, T" uniqKey="Okanoue T">T Okanoue</name>
</author>
<author><name sortKey="Shimotohno, K" uniqKey="Shimotohno K">K Shimotohno</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ji, J" uniqKey="Ji J">J Ji</name>
</author>
<author><name sortKey="Zhang, J" uniqKey="Zhang J">J Zhang</name>
</author>
<author><name sortKey="Huang, G" uniqKey="Huang G">G Huang</name>
</author>
<author><name sortKey="Qian, J" uniqKey="Qian J">J Qian</name>
</author>
<author><name sortKey="Wang, X" uniqKey="Wang X">X Wang</name>
</author>
<author><name sortKey="Mei, S" uniqKey="Mei S">S Mei</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Qin, W" uniqKey="Qin W">W Qin</name>
</author>
<author><name sortKey="Chung, Ac" uniqKey="Chung A">AC Chung</name>
</author>
<author><name sortKey="Huang, Xr" uniqKey="Huang X">XR Huang</name>
</author>
<author><name sortKey="Meng, Xm" uniqKey="Meng X">XM Meng</name>
</author>
<author><name sortKey="Hui, Ds" uniqKey="Hui D">DS Hui</name>
</author>
<author><name sortKey="Yu, Cm" uniqKey="Yu C">CM Yu</name>
</author>
<author><name sortKey="Sung, Jj" uniqKey="Sung J">JJ Sung</name>
</author>
<author><name sortKey="Lan, Hy" uniqKey="Lan H">HY Lan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Xiao, J" uniqKey="Xiao J">J Xiao</name>
</author>
<author><name sortKey="Meng, Xm" uniqKey="Meng X">XM Meng</name>
</author>
<author><name sortKey="Huang, Xr" uniqKey="Huang X">XR Huang</name>
</author>
<author><name sortKey="Chung, Ac" uniqKey="Chung A">AC Chung</name>
</author>
<author><name sortKey="Feng, Yl" uniqKey="Feng Y">YL Feng</name>
</author>
<author><name sortKey="Hui, Ds" uniqKey="Hui D">DS Hui</name>
</author>
<author><name sortKey="Yu, Cm" uniqKey="Yu C">CM Yu</name>
</author>
<author><name sortKey="Sung, Jj" uniqKey="Sung J">JJ Sung</name>
</author>
<author><name sortKey="Lan, Hy" uniqKey="Lan H">HY Lan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Van Rooij, E" uniqKey="Van Rooij E">E van Rooij</name>
</author>
<author><name sortKey="Sutherland, Lb" uniqKey="Sutherland L">LB Sutherland</name>
</author>
<author><name sortKey="Thatcher, Je" uniqKey="Thatcher J">JE Thatcher</name>
</author>
<author><name sortKey="Dimaio, Jm" uniqKey="Dimaio J">JM DiMaio</name>
</author>
<author><name sortKey="Naseem, Rh" uniqKey="Naseem R">RH Naseem</name>
</author>
<author><name sortKey="Marshall, Ws" uniqKey="Marshall W">WS Marshall</name>
</author>
<author><name sortKey="Hill, Ja" uniqKey="Hill J">JA Hill</name>
</author>
<author><name sortKey="Olson, En" uniqKey="Olson E">EN Olson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cushing, L" uniqKey="Cushing L">L Cushing</name>
</author>
<author><name sortKey="Kuang, Pp" uniqKey="Kuang P">PP Kuang</name>
</author>
<author><name sortKey="Qian, J" uniqKey="Qian J">J Qian</name>
</author>
<author><name sortKey="Shao, F" uniqKey="Shao F">F Shao</name>
</author>
<author><name sortKey="Wu, J" uniqKey="Wu J">J Wu</name>
</author>
<author><name sortKey="Little, F" uniqKey="Little F">F Little</name>
</author>
<author><name sortKey="Thannickal, Vj" uniqKey="Thannickal V">VJ Thannickal</name>
</author>
<author><name sortKey="Cardoso, Wv" uniqKey="Cardoso W">WV Cardoso</name>
</author>
<author><name sortKey="Lu, J" uniqKey="Lu J">J Lü</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Roderburg, C" uniqKey="Roderburg C">C Roderburg</name>
</author>
<author><name sortKey="Urban, Gw" uniqKey="Urban G">GW Urban</name>
</author>
<author><name sortKey="Bettermann, K" uniqKey="Bettermann K">K Bettermann</name>
</author>
<author><name sortKey="Vucur, M" uniqKey="Vucur M">M Vucur</name>
</author>
<author><name sortKey="Zimmermann, H" uniqKey="Zimmermann H">H Zimmermann</name>
</author>
<author><name sortKey="Schmidt, S" uniqKey="Schmidt S">S Schmidt</name>
</author>
<author><name sortKey="Janssen, J" uniqKey="Janssen J">J Janssen</name>
</author>
<author><name sortKey="Koppe, C" uniqKey="Koppe C">C Koppe</name>
</author>
<author><name sortKey="Knolle, P" uniqKey="Knolle P">P Knolle</name>
</author>
<author><name sortKey="Castoldi, M" uniqKey="Castoldi M">M Castoldi</name>
</author>
<author><name sortKey="Tacke, F" uniqKey="Tacke F">F Tacke</name>
</author>
<author><name sortKey="Trautwein, C" uniqKey="Trautwein C">C Trautwein</name>
</author>
<author><name sortKey="Luedde, T" uniqKey="Luedde T">T Luedde</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Friedman, Sl" uniqKey="Friedman S">SL Friedman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wright, Mc" uniqKey="Wright M">MC Wright</name>
</author>
<author><name sortKey="Issa, R" uniqKey="Issa R">R Issa</name>
</author>
<author><name sortKey="Smart, De" uniqKey="Smart D">DE Smart</name>
</author>
<author><name sortKey="Trim, N" uniqKey="Trim N">N Trim</name>
</author>
<author><name sortKey="Murray, Gi" uniqKey="Murray G">GI Murray</name>
</author>
<author><name sortKey="Primrose, Jn" uniqKey="Primrose J">JN Primrose</name>
</author>
<author><name sortKey="Arthur, Mj" uniqKey="Arthur M">MJ Arthur</name>
</author>
<author><name sortKey="Iredale, Jp" uniqKey="Iredale J">JP Iredale</name>
</author>
<author><name sortKey="Mann, Da" uniqKey="Mann D">DA Mann</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Elsharkawy, Am" uniqKey="Elsharkawy A">AM Elsharkawy</name>
</author>
<author><name sortKey="Oakley, F" uniqKey="Oakley F">F Oakley</name>
</author>
<author><name sortKey="Mann, Da" uniqKey="Mann D">DA Mann</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fang, Y" uniqKey="Fang Y">Y Fang</name>
</author>
<author><name sortKey="Yu, X" uniqKey="Yu X">X Yu</name>
</author>
<author><name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name>
</author>
<author><name sortKey="Kriegel, Aj" uniqKey="Kriegel A">AJ Kriegel</name>
</author>
<author><name sortKey="Heng, Y" uniqKey="Heng Y">Y Heng</name>
</author>
<author><name sortKey="Xu, X" uniqKey="Xu X">X Xu</name>
</author>
<author><name sortKey="Liang, M" uniqKey="Liang M">M Liang</name>
</author>
<author><name sortKey="Ding, X" uniqKey="Ding X">X Ding</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Reif, S" uniqKey="Reif S">S Reif</name>
</author>
<author><name sortKey="Lang, A" uniqKey="Lang A">A Lang</name>
</author>
<author><name sortKey="Lindquist, Jn" uniqKey="Lindquist J">JN Lindquist</name>
</author>
<author><name sortKey="Yata, Y" uniqKey="Yata Y">Y Yata</name>
</author>
<author><name sortKey="Gabele, E" uniqKey="Gabele E">E Gabele</name>
</author>
<author><name sortKey="Scanga, A" uniqKey="Scanga A">A Scanga</name>
</author>
<author><name sortKey="Brenner, Da" uniqKey="Brenner D">DA Brenner</name>
</author>
<author><name sortKey="Rippe, Ra" uniqKey="Rippe R">RA Rippe</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gentilini, A" uniqKey="Gentilini A">A Gentilini</name>
</author>
<author><name sortKey="Marra, F" uniqKey="Marra F">F Marra</name>
</author>
<author><name sortKey="Gentilini, P" uniqKey="Gentilini P">P Gentilini</name>
</author>
<author><name sortKey="Pinzani, M" uniqKey="Pinzani M">M Pinzani</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Parsons, Cj" uniqKey="Parsons C">CJ Parsons</name>
</author>
<author><name sortKey="Takashima, M" uniqKey="Takashima M">M Takashima</name>
</author>
<author><name sortKey="Rippe, Ra" uniqKey="Rippe R">RA Rippe</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Voloshenyuk, Tg" uniqKey="Voloshenyuk T">TG Voloshenyuk</name>
</author>
<author><name sortKey="Landesman, Es" uniqKey="Landesman E">ES Landesman</name>
</author>
<author><name sortKey="Khoutorova, E" uniqKey="Khoutorova E">E Khoutorova</name>
</author>
<author><name sortKey="Hart, Ad" uniqKey="Hart A">AD Hart</name>
</author>
<author><name sortKey="Gardner, Jd" uniqKey="Gardner J">JD Gardner</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yu, J" uniqKey="Yu J">J Yu</name>
</author>
<author><name sortKey="Wu, Cw" uniqKey="Wu C">CW Wu</name>
</author>
<author><name sortKey="Chu, Es" uniqKey="Chu E">ES Chu</name>
</author>
<author><name sortKey="Hui, Ay" uniqKey="Hui A">AY Hui</name>
</author>
<author><name sortKey="Cheng, As" uniqKey="Cheng A">AS Cheng</name>
</author>
<author><name sortKey="Go, My" uniqKey="Go M">MY Go</name>
</author>
<author><name sortKey="Ching, Ak" uniqKey="Ching A">AK Ching</name>
</author>
<author><name sortKey="Chui, Yl" uniqKey="Chui Y">YL Chui</name>
</author>
<author><name sortKey="Chan, Hl" uniqKey="Chan H">HL Chan</name>
</author>
<author><name sortKey="Sung, Jj" uniqKey="Sung J">JJ Sung</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yu, J" uniqKey="Yu J">J Yu</name>
</author>
<author><name sortKey="Zhang, S" uniqKey="Zhang S">S Zhang</name>
</author>
<author><name sortKey="Chu, Es" uniqKey="Chu E">ES Chu</name>
</author>
<author><name sortKey="Go, My" uniqKey="Go M">MY Go</name>
</author>
<author><name sortKey="Lau, Rh" uniqKey="Lau R">RH Lau</name>
</author>
<author><name sortKey="Zhao, J" uniqKey="Zhao J">J Zhao</name>
</author>
<author><name sortKey="Wu, Cw" uniqKey="Wu C">CW Wu</name>
</author>
<author><name sortKey="Tong, L" uniqKey="Tong L">L Tong</name>
</author>
<author><name sortKey="Zhao, J" uniqKey="Zhao J">J Zhao</name>
</author>
<author><name sortKey="Poon, Tc" uniqKey="Poon T">TC Poon</name>
</author>
<author><name sortKey="Sung, Jj" uniqKey="Sung J">JJ Sung</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Ticri/CIDE/explor/HapticV1/Data/Main/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000C43 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Merge/biblio.hfd -nk 000C43 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Ticri/CIDE |area= HapticV1 |flux= Main |étape= Merge |type= RBID |clé= PMC:4466688 |texte= microRNA-29b prevents liver fibrosis by attenuating hepatic stellate cell activation and inducing apoptosis through targeting PI3K/AKT pathway }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Merge/RBID.i -Sk "pubmed:25356754" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Merge/biblio.hfd \ | NlmPubMed2Wicri -a HapticV1
![]() | This area was generated with Dilib version V0.6.23. | ![]() |