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Updated: Sep 20, 2026
Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease with Fibrosis
Published on: July 18, 2025
AT1A-deficient mice show less severe progression of liver fibrosis induced by CCl(4)
Keishi Kanno1, Susumu Tazuma, Kazuaki Chayama
1Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Japan.
Abstract:
The renin-angiotensin system has been shown to contribute to fibrogenesis in varieties of organs, including the liver. Here, we investigated whether the angiotensin II type 1A receptor (AT1A) is implicated in the development of liver fibrosis, using AT1A-deficient and wild-type (WT) mice. After single dose of carbon tetrachloride (CCl(4)), there were no significant differences between two groups with regard to hepatic inflammation and necrosis. After 4 weeks of treatment with CCl(4), histological examination revealed that AT1A-deficient mice showed less infiltration of inflammatory cells and less severe progression of liver fibrosis compared with WT mice. These findings were accompanied by the hepatic content of hydoxyproline and the expression of alpha-smooth muscle actin (alpha SMA). The level of transforming growth factor-beta 1 (TGF-beta 1) messenger RNA was markedly higher in WT mice when compared with AT1A-deficient mice. These results confirm that signaling via AT1A plays a pivotal role in hepatic fibrogenesis.
Insights
The angiotensin II type 1A receptor (AT1A) is crucial in liver fibrosis development. Blocking AT1A signaling in mice significantly reduced liver fibrosis progression and inflammation following carbon tetrachloride exposure.
Area of Science:
- Hepatology
- Fibrosis Research
- Renal Physiology
Background:
- The renin-angiotensin system (RAS) is implicated in fibrogenesis across multiple organs.
- The specific role of the angiotensin II type 1A receptor (AT1A) in liver fibrosis remains to be fully elucidated.
Purpose of the Study:
- To investigate the involvement of the AT1A receptor in the pathogenesis of liver fibrosis.
- To compare liver fibrosis progression in AT1A-deficient mice versus wild-type (WT) mice.
Main Methods:
- Utilized AT1A-deficient and WT mice models.
- Administered a single dose of carbon tetrachloride (CCl4) followed by a 4-week treatment course.
- Assessed hepatic inflammation, necrosis, fibrosis severity, hydroxyproline content, alpha-smooth muscle actin (αSMA) expression, and transforming growth factor-beta 1 (TGF-β1) mRNA levels.
Main Results:
- No significant differences in acute hepatic inflammation or necrosis were observed between groups after a single CCl4 dose.
- AT1A-deficient mice exhibited reduced inflammatory cell infiltration and less severe liver fibrosis progression compared to WT mice after 4 weeks of CCl4 treatment.
- Lower hepatic hydroxyproline content, reduced αSMA expression, and significantly lower TGF-β1 mRNA levels were noted in AT1A-deficient mice.
Conclusions:
- Signaling through the AT1A receptor plays a critical role in promoting hepatic fibrogenesis.
- Targeting the AT1A receptor may represent a potential therapeutic strategy for mitigating liver fibrosis.
