MicroRNA-134 deactivates hepatic stellate cells by targeting TGF-beta activated kinase 1-binding protein 1

摘要

Aberrant expression of microRNAs is associated with liver fibrogenesis. We previously found that microRNA-134 (miR-134) expression was reduced in fibrosis-based hepatocarcinogenesis induced by diethylinitrosamine. Herein we investigate the role and mechanisms of miR-134 in hepatic fibrosis. Our data show that miR-134 expression is reduced in rat hepatic fibrogenesis induced by carbontetrachloride, bile duct ligation, and dimethylnitrosamine, as well as in activated hepatic stellate cells (HSCs). Moreover, miR-134 inhibited HSC proliferation, and decreased the expression of smooth muscle actin and collagen I in HSCs, whereas the miR-134 inhibitor increased HSC activation. MiR-134 also negatively regulated transforming growth factor-beta-activated kinase 1-binding protein 1 (TAB1) expression in both human and rat HSCs by directly binding to its 3' untranslated region. Importantly, TAB1 expression was significantly elevated during liver fibrogenesis and HSC activation. Knockdown of TAB1 inhibited the proliferation and fibrogenic behavior of HSCs, and significantly reduced the effect of the miR-134 inhibitor on HSC proliferation. Collectively, these data suggest that miR-134 inhibits the activation of HSCs via directly targeting TAB1, and the restoration of miR-134 or targeting TAB1 is of clinical significance in the treatment of liver fibrosis.