Inhibition of RAC1 activator DOCK2 ameliorates cholestatic liver injury via regulating macrophage polarisation and hepatic stellate cell activation.

ABSTRACT:

Background

The Rho GTPase Rac family small GTPase 1 (RAC1) is considered a promising fibrotic therapeutic target, but the role of its activator, dedicator of cytokinesis 2 (DOCK2), in liver fibrosis is largely unknown. This study aimed to investigate the expression and role of DOCK2 in cholestasis-induced liver fibrosis and to further explore the potential mechanisms.

Results

Cholestasis was induced in male C57BL/6 mice by bile duct ligation (BDL). DOCK2 knockdown was achieved by tail vein injection of adenovirus containing DOCK2-targeting shRNA. The effect of DOCK2 knockdown on cholestatic liver injury was evaluated at different time points after BDL. Hepatic DOCK2 expression gradually increased after BDL. Knockdown of DOCK2 reduced the necrotic area in BDL liver and downre

SUBMITTER: Qiu J 

PROVIDER: S-EPMC11807328 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature