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<p>Bile acids (BA) interact with hepatocytes and facilitate liver regeneration, however, their interaction with liver sinusoidal endothelial cells (LSECs) during regeneration remains elusive. We investigated BA composition in two-thirds partial hepatectomy (PHx) rat models and human donors undergoing hepatectomy by mass spectrometry. We studied effects of differentially expressed BA on LSECs, in several in vitro and in vivo experiments. Results revealed that secondary BA were significantly increased in peripheral serum of both PHx models and human donors at day 2 post-PHx compared to controls. In vitro, lithocholic acid (LCA) enhanced expression of endothelial cell specific transcription factor, Id1 along with angiocrine factors, HGF and Wnt2 in LSECs. LSECs treated with TGR5-siRNA in vitro and from in vivo antibiotic-treated PHx animals showed decreased expression of Id1 and angiocrine factors. The study unveils that LCA drives Id1-TGR5 angiocrine pathway and activates release of Wnt2 and HGF in LSECs facilitating early liver regeneration.</p>

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Lithocholic acid facilitates release of angiocrine factors by liver sinusoidal endothelial cells during liver regeneration

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月30日

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  • Impreet Kaur,
  • Aarti Sharma,
  • Pinky Juneja,
  • Rajnish Tiwari,
  • Ashwini Vasudevan,
  • Hami Hemati,
  • Akash K. Mourya,
  • Viniyendra Pamecha,
  • Mlitz Veronika,
  • Claudia Fuchs,
  • Michael Trauner,
  • Shiv K. Sarin,
  • Dinesh M. Tripathi,
  • Savneet Kaur

摘要

Bile acids (BA) interact with hepatocytes and facilitate liver regeneration, however, their interaction with liver sinusoidal endothelial cells (LSECs) during regeneration remains elusive. We investigated BA composition in two-thirds partial hepatectomy (PHx) rat models and human donors undergoing hepatectomy by mass spectrometry. We studied effects of differentially expressed BA on LSECs, in several in vitro and in vivo experiments. Results revealed that secondary BA were significantly increased in peripheral serum of both PHx models and human donors at day 2 post-PHx compared to controls. In vitro, lithocholic acid (LCA) enhanced expression of endothelial cell specific transcription factor, Id1 along with angiocrine factors, HGF and Wnt2 in LSECs. LSECs treated with TGR5-siRNA in vitro and from in vivo antibiotic-treated PHx animals showed decreased expression of Id1 and angiocrine factors. The study unveils that LCA drives Id1-TGR5 angiocrine pathway and activates release of Wnt2 and HGF in LSECs facilitating early liver regeneration.