Related Experiment Video For Liver fibrosis
Updated: Sep 9, 2025
Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
A PBX1-IL7R axis mediates liver fibrosis in non-alcoholic fatty liver disease
Zhen Yang1, Jinbo Zhang2, Qihang Wang2
1Graduate School of Dalian Medical University, Dalian Medical University, Dalian, China; Department of Hepatobiliary Surgery, Changzhou No.2 People's Hospital and the third Affiliated Hospital of Nanjing Medical University, Changzhou, China.
Aims:
Non-alcoholic fatty liver disease (NAFLD), also known as metabolic dysfunction associated steatotic liver disease (MASLD), represents a spectrum of chronic liver diseases that eventually lead to cirrhosis and hepatocellular carcinoma. Liver fibrosis is both a pathological feature and a contributing factor in NAFLD. In the present study we investigated whether targeting pre-B cell leukemia transcription factor 1 (PBX1) and interleukin 7 receptor (IL7R) might ameliorate liver fibrosis in the context of NAFLD.
Methods And Materials:
NAFLD was induced in C57/B6j mice by feeding with a choline-deficient amino acid defined high-fat diet (CDAA-HFD).
Key Findings:
Both PBX1 expression and IL7R expression were up-regulated in hepatic stellate cells (HSCs) isolated from the mice fed the CDAA-HFD compared to those isolated from the control mice. Myofibroblast-specific PBX1 depletion, by injecting the mice with AAV6 carrying short-hairpin RNA (shRNA) against PBX1, significantly attenuated liver fibrosis induced by CDAA-HFD feeding. Similarly, myofibroblast-specific IL7R depletion significantly mitigated NAFLD-associated liver fibrosis. Of note, liver injury and steatosis were not influenced by either PBX1 or IL7R depletion. Importantly, IL7R blockade with a neutralizing antibody likewise diminished NAFLD-associated liver fibrosis. Finally, a positive correlation between PBX1 expression, IL7R expression, and myofibroblast activation was identified in liver specimens from NAFLD patients.
Significance:
Our data demonstrate the feasibility of targeting the PBX1-IL7R axis for the intervention of NAFLD-associated liver fibrosis.
