CD47 Deficiency in Mice Exacerbates Chronic Fatty Diet-Induced Steatohepatitis Through Its Role in Regulating Hepatic Inflammation and Lipid Metabolism.

Frontiers in Immunology
Hui-Chao TaoYong-Guang Yang

Abstract

Inflammation is one of the hallmarks of non-alcoholic steatohepatitis. CD47 is a widely expressed transmembrane protein that signals through inhibitory receptor signal regulatory protein α (SIRPα) to inhibit macrophage activation and phagocytosis. In this study, we sought to investigate the role of CD47 in hepatosteatosis and fibrosis induced by a chronic high-fat diet (HFD), by comparing disease development in wild-type (WT) and CD47KO mice fed HFD for 40 weeks. The HFD induced remarkably more severe hepatic steatosis and fibrosis but less body weight gain and less subcutaneous fat accumulation in CD47KO mice compared to WT mice. Liver tissues from HFD-fed CD47KO mice exhibited enhanced inflammation characterized by increased proinflammatory cytokine production and increased nuclear factor-κB (NF-κB) activation compared to similarly fed WT mice. Although higher expression of apolipoproteins was observed in CD47KO mice compared to WT mice under a low-fat diet (LFD), HFD-fed WT and CD47KO mice showed comparably prominent downregulation of these apolipoprotein genes, suggesting that the marked difference observed in lipid accumulation and hepatosteatosis between these mice cannot be explained by changes in apolipoproteins. Like a...Continue Reading

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Citations

May 1, 2021·International Journal of Molecular Sciences·Atharva KaleKedar Ghimire

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Datasets Mentioned

BETA
AF5006

Methods Mentioned

BETA
ELISA
Assay
PCR
nuclear translocation

Software Mentioned

Prism
GraphPad
Zeiss
Image Pro Plus

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