miR-12135 ameliorates liver fibrosis accompanied with the downregulation of integrin subunit alpha 11.

ABSTRACT

Cirrhosis is becoming one of the most common diseases worldwide. Abnormal upregulation of transforming growth factor ß (TGF-ß) signaling plays a pivotal role in the excess activation of hepatic stellate cells. However, an efficient countermeasure against abnormal hepatic stellate cell activation is yet to be established because TGF-ß signaling is involved in several biological processes. Herein, we demonstrated the antifibrotic effect of miR-12135, a microRNA with unknown function upregulated by isoflavone. Comprehensive transcriptome assay demonstrated that miR-12135 suppressed Integrin Subunit Alpha 11 (ITGA11) and that ITGA11 expression is correlated with alpha smooth muscle actin expression in patients with cirrhosis. miR-12135 suppressed the expression level of ITGA11 and liver fibrosis. Importantly, ITGA11 is overexpressed in activated hepatic stellate cells, whereas ITGA11 knockout mice are viable and fertile. In conclusions, the miR-12135/ITGA11 axis can be an ideal therapeutic target to suppress fibrosis by precisely targeting abnormally upregulated TGF-ß signaling in hepatic stellate cells.