Scholarlink

<p>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. Cholestatic patient liver samples also show elevated Myc and P-selectin in ECs, along with increased neutrophils. The findings identify ECs as key drivers of cholestatic liver injury through a Myc-driven program and suggest that targeting the CDCA/FXR/Myc/P-selectin axis may offer a therapeutic approach.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月1日

查看全文
  • Peng Zhang,
  • Xinying Li,
  • Jinyuan Liang,
  • Yuanwen Zheng,
  • Yao Tong,
  • Jing Shen,
  • Yatai Chen,
  • Penghu Han,
  • Shuzheng Chu,
  • Ruirui Liu,
  • Mengqi Zheng,
  • Yunjiao Zhai,
  • Xiaolong Tang,
  • Cuijuan Zhang,
  • Hui Qu,
  • Ping Mi,
  • Jin Chai,
  • Detian Yuan,
  • Shiyang Li

摘要

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. Cholestatic patient liver samples also show elevated Myc and P-selectin in ECs, along with increased neutrophils. The findings identify ECs as key drivers of cholestatic liver injury through a Myc-driven program and suggest that targeting the CDCA/FXR/Myc/P-selectin axis may offer a therapeutic approach.