Lithocholic acid facilitates release of angiocrine factors by liver sinusoidal endothelial cells during liver regeneration
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.
Authors
- Aarti Sharma (ORCID: https://orcid.org/0000-0002-7186-6974)
- Hamed Hemati (ORCID: https://orcid.org/0000-0001-6436-5111)
- Akash K. Mourya
- Shiv Kumar Sarin (ORCID: https://orcid.org/0000-0002-0544-5610)
- Pinky Juneja
- Ashwini Vasudevan (ORCID: https://orcid.org/0000-0001-5310-8662)
- Rajnish Tiwari (ORCID: https://orcid.org/0000-0002-7510-4010)
- Michael A Trauner (ORCID: https://orcid.org/0000-0002-1275-6425)
- Dinesh Mani Tripathi (ORCID: https://orcid.org/0000-0003-0897-6959)
- Impreet Kaur
- Savneet Kaur (ORCID: https://orcid.org/0000-0002-9863-2772)
- Claudia Fuchs (ORCID: https://orcid.org/0000-0002-0636-1320)
- Mlitz Veronika
- Viniyendra Pamecha
Institutions
- University of Kentucky (US)
- Amity University (IN)
- National Institute of Pharmaceutical Education and Research - Ahmedabad (IN)
- Institute of Liver and Biliary Sciences (IN)
- Medical University of Vienna (AT)
Publication Details
- Journal
- npj gut and liver.
- Published
- 2025-09-30
- DOI
- https://doi.org/10.1038/s44355-025-00034-y
- Citations
- 1
- Primary Topic
- Liver physiology and pathology
- Type
- article
- Field-Weighted Citation Impact
- 1.32
Funders
- American Association for the Study of Liver Diseases
- Department of Science and Technology, Ministry of Science and Technology, India
- Indian Council of Medical Research
- Bundesministerium für Wissenschaft und Forschung
- Science and Engineering Research Board