Related Experiment Video
Updated: Jun 30, 2025
08:56
Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
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Sortilin in Biliary Epithelial Cells Promotes Ductular Reaction and Fibrosis during Cholestatic Injury
Einav Hubel1, Anat Neumann1, Sigal Fishman1
1The Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center and Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
The American Journal of Pathology
|March 17, 2024
Summary
Sortilin protein is crucial for biliary epithelial cell proliferation and new duct formation during cholestatic liver injury. Targeting sortilin may reduce fibrosis development in these conditions.
Area of Science:
- Hepatology
- Cell Biology
- Molecular Biology
Background:
- Cholestatic liver injury involves biliary epithelial cell (BEC) proliferation, ductular reaction, and fibrosis.
- Sortilin (Sort1) influences interleukin-6 (IL-6) secretion and leukemia inhibitory factor (LIF) signaling.
Purpose of the Study:
- To investigate the role of sortilin in cholestatic injury-induced ductular reaction, morphogenesis, and fibrosis.
- To elucidate the interplay between sortilin, IL-6, and LIF signaling in BECs during liver injury.
Main Methods:
- Bile duct ligation (BDL) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet induced cholestatic injury in wild-type, Sort1 knockout, and BEC-specific sortilin knockout mice.
- Administration of IL-6 or LIF was used to assess rescue effects.
- BEC proliferation, ductular reaction, morphogenesis, fibrosis, and signaling pathways (pSTAT3) were analyzed.
Main Results:
- Sortilin deficiency in mice reduced BEC proliferation, ductular reaction, and morphogenesis.
- LIF administration restored BEC proliferation and morphogenesis in Sort1-deficient mice.
- Sortilin is essential for LIF receptor/gp130 signaling activation in BECs, not IL-6 secretion.
- BEC-specific sortilin deficiency diminished fibrosis development.
Conclusions:
- Sortilin-mediated LIF signaling in BECs drives ductular reaction and morphogenesis in cholestatic liver injury.
- BEC sortilin plays a pivotal role in promoting fibrosis during cholestatic conditions.
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