Kindlin-2 maintains liver homeostasis by regulating GSTP1-OPN-mediated oxidative stress and inflammation in mice.

ABSTRACT: Hepatocyte plays a principal role in preserving integrity of the liver homeostasis. Our recent study demonstrated that Kindlin-2, a focal adhesion protein that activates integrins and regulates cell-extracellular matrix interactions, plays an important role in regulation of liver homeostasis by inhibiting inflammation pathway; however, the molecular mechanism of how Kindlin-2 KO activates inflammation is unknown. Here, we show that Kindlin-2 loss largely downregulates the antioxidant glutathione-S-transferase P1 in hepatocytes by promoting its ubiquitination and degradation via a mechanism involving protein-protein interaction. This causes overproduction of intracellular reactive oxygen species and excessive oxidative stress in hepatocytes. Kindlin-2 loss upregulates osteopontin in hepatoc

SUBMITTER: Zhong Y 

PROVIDER: S-EPMC10831259 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature