Kindlin-2 regulates hepatic stellate cells activation and liver fibrogenesis.

ABSTRACT: Liver fibrosis, the common response associated with chronic liver diseases, ultimately leads to cirrhosis, a major public health problem worldwide. Activation of hepatic stellate cells (HSCs) by transforming growth factor (TGF)-?1 is a key step in liver fibrosis. Here we report that Kindlin-2 expression is elevated in the livers of mice with experimental liver fibrosis and also in the livers of patients with liver fibrosis. TGF-?1 increases Kindlin-2 expression in cultured HSCs in a p38 and ERK mitogen-activated protein kinase (MAPK)-dependent manner, partly. More importantly, Kindlin-2 deficiency significantly attenuated mouse liver fibrosis and HSC activation. Mechanistically, Kindlin-2 promotes TGF-? signaling through upregulation of Smad2 and Smad3 phosphorylation. Our work demonstrates an important role for Kindlin-2 in liver fibrosis, and inhibiting Kindlin-2 in the livers may represent a novel strategy to treat liver fibrosis.

SUBMITTER: Yu J 

PROVIDER: S-EPMC6135746 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature