Kwiecinski, Monika, Noetel, Andrea, Elfimova, Natalia, Trebicka, Jonel ORCID: 0000-0002-7028-3881, Schievenbusch, Stephanie, Strack, Ingo, Molnar, Levente, von Brandenstein, Melanie, Toex, Ulrich, Nischt, Roswitha, Coutelle, Oliver, Dienes, Hans Peter and Odenthal, Margarete (2011). Hepatocyte Growth Factor (HGF) Inhibits Collagen I and IV Synthesis in Hepatic Stellate Cells by miRNA-29 Induction. PLoS One, 6 (9). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

Full text not available from this repository.

Abstract

Background: In chronic liver disease, hepatic stellate cells (HSC) transdifferentiate into myofibroblasts, promoting extracellular matrix (ECM) synthesis and deposition. Stimulation of HSC by transforming growth factor-beta (TGF-beta) is a crucial event in liver fibrogenesis due to its impact on myofibroblastic transition and ECM induction. In contrast, hepatocyte growth factor (HGF), exerts antifibrotic activities. Recently, miR-29 has been reported to be involved in ECM synthesis. We therefore studied the influence of HGF and TGF-beta on the miR-29 collagen axis in HSC. Methodology: HSC, isolated from rats, were characterized for HGF and Met receptor expression by Real-Time PCR and Western blotting during culture induced myofibroblastic transition. Then, the levels of TGF-beta, HGF, collagen-I and -IV mRNA, in addition to miR-29a and miR-29b were determined after HGF and TGF-beta stimulation of HSC or after experimental fibrosis induced by bile-duct obstruction in rats. The interaction of miR-29 with 3'-untranslated mRNA regions (UTR) was analyzed by reporter assays. The repressive effect of miR-29 on collagen synthesis was studied in HSC treated with miR-29-mimicks by Real-Time PCR and immunoblotting. Principal Findings: The 3'-UTR of the collagen-1 and -4 subtypes were identified to bind miR-29. Hence, miR-29a/b overexpression in HSC resulted in a marked reduction of collagen-I and -IV synthesis. Conversely, a decrease in miR-29 levels is observed during collagen accumulation upon experimental fibrosis, in vivo, and after TGF-beta stimulation of HSC, in vitro. Finally, we show that during myofibroblastic transition and TGF-beta exposure the HGF-receptor, Met, is upregulated in HSC. Thus, whereas TGF-beta stimulation leads to a reduction in miR-29 expression and de-repression of collagen synthesis, stimulation with HGF was definitely associated with highly elevated miR-29 levels and markedly repressed collagen-I and -IV synthesis. Conclusions: Upregulation of miRNA-29 by HGF and downregulation by TGF-beta take part in the anti-or profibrogenic response of HSC, respectively.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kwiecinski, MonikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noetel, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Elfimova, NataliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trebicka, JonelUNSPECIFIEDorcid.org/0000-0002-7028-3881UNSPECIFIED
Schievenbusch, StephanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Strack, IngoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Molnar, LeventeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Brandenstein, MelanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toex, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nischt, RoswithaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coutelle, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dienes, Hans PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Odenthal, MargareteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-489144
DOI: 10.1371/journal.pone.0024568
Journal or Publication Title: PLoS One
Volume: 6
Number: 9
Date: 2011
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1932-6203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
BETA GENE-EXPRESSION; FAT-STORING CELLS; RAT-LIVER; TRANSFORMING GROWTH-FACTOR-BETA-1; TGF-BETA; FACTOR SUPPRESSES; FIBROSIS; ACTIVATION; MICRORNAS; TRANSDIFFERENTIATIONMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/48914

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item