Roderburg, Christoph and Luedde, Mark and Cardenas, David Vargas and Vucur, Mihael and Mollnow, Tobias and Zimmermann, Henning W. and Koch, Alexander and Hellerbrand, Claus and Weiskirchen, Ralf and Frey, Norbert and Tacke, Frank and Trautwein, Christian and Luedde, Tom (2013) miR-133a mediates TGF-beta-dependent derepression of collagen synthesis in hepatic stellate cells during liver fibrosis. JOURNAL OF HEPATOLOGY, 58 (4). pp. 736-742. ISSN 0168-8278,
Full text not available from this repository. (Request a copy)Abstract
Background & Aims: miRNAs are novel regulators of organ fibrosis. miR-133a plays a role in cardiac and muscle remodeling, but its function in the liver is unclear. We therefore aimed at evaluating a possible function of miR-133a in hepatofibrogenesis. Methods: miR-133a levels were measured in whole liver samples from different murine hepatic fibrosis models and human liver tissue from patients with liver cirrhosis. The cell-specific regulation of miR-133a was assessed in FACS-sorted hepatic cell sub-populations. Murine and human primary hepatic stellate cells (HSC) were isolated and treated with different cytokines to evaluate upstream regulators of miR-133a. Moreover, GRX cells were transfected with synthetic miR-133a and the effect on extracellular matrix (ECM) gene regulation was assessed. Finally, miR-133a serum levels were measured in a cohort of patients with chronic liver diseases and correlated with disease progression. Results: Overall miR-133a expression levels were unchanged in whole RNA extracts from fibrotic murine and human livers. However, miR-133a was specifically downregulated in HSC during fibrogenesis. Treatment of primary murine and human HSC with transforming growth factor (TGF)-beta resulted in a significant downregulation of miR-133a in these cells. In turn, overexpression of miR-133a in primary murine HSC led to decreased expression of collagens. In addition, miR-133a serum levels were increased in patients with chronic liver disease and indicated the presence and progression of liver cirrhosis. Conclusions: Evidence is presented for a novel antifibrotic functional role of miR-133a in hepatofibrogenesis. miR-133a may thus represent a target for diagnostic and therapeutic strategies in liver fibrosis. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEPATOCELLULAR-CARCINOMA; MYOCARDIAL FIBROSIS; MICRORNAS; MIR-29; CULTURE; EXPRESSION; REVEALS; INJURY; LINE; RNAS; miRNA; miR-133a; Hepatic stellate cells; TGF-beta; Liver fibrosis; miR-29 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Apr 2020 04:37 |
| Last Modified: | 20 Apr 2020 04:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/16905 |
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