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Updated: Oct 4, 2025
Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
FSTL1 promotes liver fibrosis by reprogramming macrophage function through modulating the intracellular function of
Jianhua Rao1,2,3, Hao Wang4,2, Ming Ni4,2
1Hepatobiliary Center of The First Affiliated Hospital, Nanjing Medical University; Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, Jiangsu, China lvling@njmu.edu.cn docchengfeng@njmu.edu.cn raojh@njmu.edu.cn.
Macrophage Follistatin-like protein 1 (FSTL1) drives liver fibrosis by promoting M1 polarization and inflammation. Blocking FSTL1 in myeloid cells reduces liver fibrosis progression and inflammation.
Area of Science:
- Immunology
- Hepatology
- Molecular Biology
Background:
- Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein with largely uncharacterized roles in inflammatory diseases.
- The specific involvement of macrophage-derived FSTL1 in the pathogenesis of liver fibrosis remains to be elucidated.
Purpose of the Study:
- To investigate the role of macrophage FSTL1 in the development and progression of liver fibrosis.
- To elucidate the underlying molecular mechanisms by which macrophage FSTL1 influences liver fibrosis.
Main Methods:
- Expression analysis of FSTL1 in human liver samples from fibrosis patients and controls.
- Generation and utilization of myeloid-specific FSTL1-knockout (FSTL1M-KO) mice in three distinct murine models of liver fibrosis.
- In vitro and in vivo assessment of macrophage polarization, inflammatory responses, and the FSTL1-PKM2 interaction.
Main Results:
- FSTL1 expression is significantly upregulated in macrophages within fibrotic livers of humans and mice.
- Myeloid-specific FSTL1 deficiency markedly attenuated liver fibrosis progression, reducing inflammatory cell infiltration and pro-inflammatory factor expression.
- FSTL1 deficiency suppressed M1 macrophage polarization and NF-κB pathway activation; FSTL1 directly binds to PKM2, promoting its phosphorylation, nuclear translocation, and glycolysis, thereby enhancing M1 polarization and inflammation.
Conclusions:
- Macrophage FSTL1 is a key driver of liver fibrosis progression.
- FSTL1 promotes liver fibrosis by inducing M1 macrophage polarization and inflammation via intracellular PKM2 reprogramming.
- Targeting macrophage FSTL1 represents a potential therapeutic strategy for liver fibrosis.
