| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2775259 | Experimental and Molecular Pathology | 2011 | 5 Pages |
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 non-alcoholic 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.
► Adiponectin protects from inflammation and fibrosis in metabolic liver disease, and here it is shown that this adipokine induces matrix metalloproteinase-9 (MMP-9) mRNA and activity in primary human hepatocytes (PHH). ► MMP-9 activity is increased in two models of non-alcoholic stetaohepatitis but is not altered in simple fatty liver. ► MMP-9 activity even negatively correlates with adiponectin serum levels in a murine model of non-alcoholic stetaohepatitis.
