RXR<i>α</i> modulates hepatic stellate cell activation and liver fibrosis by targeting CaMKK<i>β</i>-AMPK<i>α</i> axis.

ABSTRACT: Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal mo

SUBMITTER: Cai L 

PROVIDER: S-EPMC12278412 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature