MMP-9 activity is increased by adiponectin in primary human hepatocytes but even negatively correlates with serum adiponectin in a rodent model of non-alcoholic steatohepatitis

Wanninger, Josef and Walter, Roland and Bauer, Sabrina and Eisinger, Kristina and Schaeffler, Andreas and Dorn, Christoph and Weiss, Thomas S. and Hellerbrand, Claus and Buechler, Christa (2011) MMP-9 activity is increased by adiponectin in primary human hepatocytes but even negatively correlates with serum adiponectin in a rodent model of non-alcoholic steatohepatitis. EXPERIMENTAL AND MOLECULAR PATHOLOGY, 91 (2). pp. 603-607. ISSN 0014-4800,

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Abstract

Adiponectin protects from inflammation and fibrosis in metabolic liver disease. In the present study we analyzed whether this adipokine may directly affect the activity of matrix metalloproteinases (MMPs), central regulators of fibrinolysis, in hepatocytes. Global gene expression analysis indicated upregulation of MMP-9 and tissue inhibitor of metalloproteinases-1 (TIMP-1) expression in primary human hepatocytes (PHH) in response to stimulation with adiponectin, and these results were confirmed by real-time RT-PCR. Furthermore, gelatin zymography revealed that MMP-9 activity was significantly induced in supernatants of adiponectin stimulated PHHs. In a murine model of hepatic steatosis and in human steatotic liver samples hepatic MMP-9 activity was not significantly altered. However, in two different murine models of nonalcoholic steatohepatitis (NASH) MMP-9 activity was significantly elevated compared to chow fed control mice. Of note, MMP-9 activity did not or even negatively, respectively, correlate with adiponectin serum levels in these models. The current data indicate that in NASH hepatic inflammation and fibrosis but not hepatic steatosis induce liver MMP-9 activity, and this induction seems to be related to the anti-inflammatory activity of adiponectin rather than its effect on hepatocellular MMP-9 expression. (C) 2011 Elsevier Inc. All rights reserved.

Item Type: Article
Uncontrolled Keywords: FATTY LIVER-DISEASE; MATRIX METALLOPROTEINASES; ATHEROGENIC DIET; EXPRESSION; MICE; FIBROSIS; ACTIVATION; TISSUE; ALPHA; MOUSE; Liver fibrosis; Extracellular matrix; Paigen diet; Hepatic steatosis
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Medicine > Lehrstuhl für Kinder- und Jugendmedizin
Depositing User: Dr. Gernot Deinzer
Date Deposited: 28 May 2020 09:59
Last Modified: 28 May 2020 09:59
URI: https://pred.uni-regensburg.de/id/eprint/20054

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