BioProject

Infiltration and activation of macrophages are key events in acute liver injury (ALI). More...

Infiltration and activation of macrophages are key events in acute liver injury (ALI). The voltage-gated potassium channel subunit, Kv1.3, plays a crucial role in regulating the immunologic function of macrophages and is widely recognized as a potential therapeutic target for immunotherapy. Herein, we hypothesized that blockage of Kv1.3 may influence ALI through inhibiting macrophages infiltration in damaged liver tissues. We established a mouse model of ALI via LPS+D-GAIN treatment. Margatoxin was administered into the peritoneal cavity of ALI mice and the impact of this treatment on ALI and macrophage migration in vivo and in vitro was done via immunohistochemistry, Transwell migration, and wound healing assays. To understand the mechanism by which Kv1.3 inhibitor could alleviate liver injury, RNA-seq profiling analysis and functional assays were performed. MgTX treatment alleviated ALI in mice, as evidenced by reduced macrophage infiltration in liver tissues and lower serum levels of liver ALT and AST. RNA-seq profiling analysis showed that the most obvious change was in δ-catenin, which was associated with macrophage migration and downregulated by MgTX treatment and confirmed by Transwell and wound healing assay. Overexpression of δ-catenin in RAW264.7 promoted migration, an event that was suppressed upon silencing of δ-catenin. Mechanistically, the expression of RhoA was regulated by the overexpression or knockdown of δ-catenin, while no significant change in expression of Cdc42 and Rac1 was observed. These findings suggest a role for blockage of Kv1.3 channel in macrophage migration and reveal a novel target in the treatment of liver diseases. Less...