Chenodeoxycholic acid modulates cholestatic niche through FXR/Myc/P-selectin axis in liver endothelial cells.

ABSTRACT: Cholestatic liver diseases are characterized by excessive bile acid accumulation in the liver. Endothelial cells (ECs) shape the local microenvironment in both normal conditions and liver injury, yet their role in cholestasis is unclear. Through a comparative analysis of single-cell RNA sequencing data from various murine models of liver injury, we identify distinctive Myc activation within ECs during obstructive cholestasis resulting from bile duct ligation (BDL). Myc overexpression in ECs significantly upregulates P-selectin, increasing neutrophil infiltration and worsening cholestatic liver injury. This process occurs through the FXR, activated by chenodeoxycholic acid (CDCA) and its conjugate TCDCA. Inhibiting P-selectin with PSI-697 reduces neutrophil recruitment and alleviates injury

SUBMITTER: Zhang P 

PROVIDER: S-EPMC11873286 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature