Autophagy-Related Activation of Hepatic Stellate Cells Reduces Cellular miR-29a by Promoting Its Vesicular Secretion
Xiaojie Yu, N Elfimova, Marion Müller, Daniel Bachurski, Ulrike Koitzsch, Uta Drebber, Esther Mahabir, Hinrich P. Hansen, Scott L. Friedman, Sabine Klein, Hans Peter Dienes, Marianna Hösel, Reinhard Buettner, Jonel Trebicka, Vangelis Kondylis, Inge Mannaerts, Margarete Odenthal
Abstract
BACKGROUND & AIMS: Liver fibrosis arises from long-term chronic liver injury, accompanied by an accelerated wound healing response with interstitial accumulation of extracellular matrix (ECM). Activated hepatic stellate cells (HSC) are the main source for ECM production. MicroRNA29a (miR-29a) is a crucial antifibrotic miRNA that is repressed during fibrosis, resulting in up-regulation of collagen synthesis. METHODS: induced liver fibrosis model. RESULTS: -treated murine liver fibrosis and specimens of hepatitis C virus patients with chronic liver disease. CONCLUSIONS: We provide evidence that activation-associated autophagy in HSC induces release of miR-29a, whereas inhibition of autophagy represses fibrogenic gene expression in part through attenuated miR-29a secretion.