The effect of C5aR1 deletion on gene expression in liver of NASH mice

Published: 12 January 2023| Version 1 | DOI: 10.17632/j8v2c8z7zt.1
Fudi Zhong


Mice were subjected to a WD combined with a low weekly dose of intraperitoneal carbon tetrachloride (CCl4) for 12 weeks as described previously, resulting in a rapid progression to NASH with fibrosis. C5aR1−/− and wild type mice were maintained on the NASH model of WD+CCl4 to functionally validate the effects of C5aR1 on the development of NASH. Histopathology and Sirius red staining revealed that C5aR1 deficiency alleviated the fibrosis level in NASH mice. Moreover, the expression of pro-fibrotic markers, such as a-Sma, Col1a1, and Tgf-b1 was diminished in the liver tissue of C5aR1 deleted mice. Again, the mRNA levels of inflammation associated genes Tnf-a, IL-6 and IL-1b were downregulated in C5aR1 deficient mice compared with WT mice. In addition, Oil Red O staining analysis showed that lipid droplets were reduced in C5aR1−/− mice compared to WT mice. C5aR1 deletion markedly decreased the expression of lipid metabolic genes in liver, such as Srebf1, Acc and Fasn. Taken together, loss of C5aR1 inhibits the progression of NASH, including resistance to steatosis, inflammation, and fibrosis. Reference Tsuchida T, Lee YA, Fujiwara N, Ybanez M, Allen B, Martins S, et al. A simple diet- and chemical-induced murine NASH model with rapid progression of steatohepatitis, fibrosis and liver cancer. J Hepatol 2018,69:385-395.



Guangxi Medical University


Innate Immunity, Non-Alcoholic Fatty Liver Disease