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Updated: Jun 23, 2026
07:27
The Murine Choline-Deficient, Ethionine-Supplemented (CDE) Diet Model of Chronic Liver Injury
Published on: October 21, 2017
CCR2 promotes hepatic fibrosis in mice
Ekihiro Seki1, Samuele de Minicis, Sayaka Inokuchi
1Department of Medicine, University of California, San Diego, School of Medicine, La Jolla, CA 92093-0702, USA. ekseki@ucsd.edu
Hepatology (Baltimore, Md.)
|May 15, 2009
Summary
Chemokine receptor CCR2 (C-C chemokine receptor type 2) drives hepatic fibrosis by promoting hepatic stellate cell (HSC) migration. Blocking CCR2 significantly reduces liver fibrosis, highlighting its therapeutic potential.
Area of Science:
- Hepatology
- Immunology
- Fibrosis Research
Background:
- Chemokines and their receptors mediate cell migration crucial for liver fibrogenesis.
- Hepatic stellate cells (HSCs) and Kupffer cells are key players in liver fibrosis development.
Purpose of the Study:
- To investigate the role of CCR2 (C-C chemokine receptor type 2) in hepatic fibrosis.
- To determine the cellular source and functional significance of CCR2 in liver injury and fibrogenesis.
Main Methods:
- Utilized bile duct ligation (BDL) and carbon tetrachloride (CCl4) models of liver fibrosis in wild-type and CCR2 knockout mice.
- Generated CCR2 chimeric mice to distinguish the roles of CCR2 in bone marrow-derived cells versus resident liver cells.
- Performed in vitro assays to assess HSC response to chemokines (MCP-1, MCP-2, MCP-3) in the absence of CCR2 or p47phox.
Main Results:
- CCR2, MCP-1, MCP-2, and MCP-3 expression increased in liver injury models.
- CCR2 deficiency markedly reduced liver fibrosis, collagen deposition, and alpha-smooth muscle actin expression.
- CCR2 on resident liver cells, particularly HSCs, was essential for fibrogenic responses, while its role in bone marrow-derived cells was more prominent in early injury phases.
Conclusions:
- CCR2 signaling is critical for hepatic stellate cell chemotaxis and migration.
- CCR2 plays a significant role in the pathogenesis of hepatic fibrosis.
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