Wobser, Hella and Dorn, Christoph and Weiss, Thomas S. and Amann, Thomas and Bollheimer, Cornelius and Buettner, Roland and Schoelmerich, Juergen and Hellerbrand, Claus (2009) Lipid accumulation in hepatocytes induces fibrogenic activation of hepatic stellate cells. CELL RESEARCH, 19 (8). pp. 996-1005. ISSN 1001-0602, 1748-7838
Full text not available from this repository. (Request a copy)Abstract
Despite the initial belief that non-alcoholic fatty liver disease is a benign disorder, it is now recognized that fibrosis progression occurs in a significant number of patients. Furthermore, hepatic steatosis has been identified as a risk factor for the progression of hepatic fibrosis in a wide range of other liver diseases. Here, we established an in vitro model to study the effect of hepatic lipid accumulation on hepatic stellate cells (HSCs), the central mediators of liver fibrogenesis. Primary human hepatocytes were incubated with the saturated fatty acid palmitate to induce intracellular lipid accumulation. Subsequently, human HSCs were incubated with conditioned media (CM) from steatotic or control hepatocytes. Lipid accumulation in hepatocytes induced the release of factors that accelerated the activation and proliferation of HSC, and enhanced their resistance to apoptosis, largely mediated via activation of the PI-3-kinase pathway. Furthermore, CM from steatotic hepatocytes induced the expression of the profibrogenic genes TGF-beta, tissue inhibitor of metallo-proteinase-1 (TIMP-1), TIMP-2 and matrix-metallo-proteinase-2, as well as nuclear-factor kappa B-dependent MCP-1 expression in HSC. In summary, our in vitro data indicate a potential mechanism for the pathophysiological link between hepatic steatosis and fibrogenesis in vivo. Herewith, this study provides an attractive in vitro model to study the molecular mechanisms of steatosis-induced fibrogenesis, and to identify and test novel targets for antifibrotic therapies in fatty liver disease.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NONALCOHOLIC FATTY LIVER; I COLLAGEN EXPRESSION; NF-KAPPA-B; HEPATOCELLULAR-CARCINOMA; CRYPTOGENIC CIRRHOSIS; NATURAL-HISTORY; FIBROSIS; STEATOHEPATITIS; RAT; APOPTOSIS; fibrosis; hepatic stellate cells; non-alcoholic fatty liver disease; steatosis; in vitro model |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Sep 2020 07:23 |
| Last Modified: | 10 Sep 2020 07:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28589 |
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