Aggf1 attenuates hepatic inflammation and activation of hepatic stellate cells by repressing Ccl2 transcription

Abstract

Liver injury represents a continuum of pathophysiological processes involving a complex interplay between hepatocytes, macrophages, and hepatic stellate cells. The mechanism whereby these intercellular interactions contribute to liver injury and fibrosis is not completely understood. We report here that angiogenic factor with G patch and FHA domains 1 (Aggf1) was downregulated in the livers of cirrhotic patients compared to healthy controls and in primary hepatocytes in response to carbon tetrachloride (CCl4) stimulation. Overexpression of Aggf1 attenuated macrophage chemotaxis. Aggf1 interacted with NF-κB to block its binding to the Ccl2 gene promoter and repressed Ccl2 transcription in hepatocytes. Macrophages cultured in the conditioned media collected from Aggf1-overexpressing hepatocytes antagonized HSC activation. Taken together, our data illustrate a novel role for Aggf1 in regulating hepatic inflammation and provide insights on the development of interventional strategies against cirrhosis.

Keywords

Aggf1 / liver fibrosis / hepatocyte / hepatic stellate cell / macrophage

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Acknowledgements

This work was supported, in part, by grants from the Natural Science Foundation of China (81402550), the Natural Science Foundation of Jiangsu Province (BK20140906), the Natural Science Foundation of Jiangsu Higher Education Institutions (14KJB310007), and the Science & Technology Development Foundation of Nanjing Medical University (2013NJMU015). Wenping Xu received funding from Jiangsu Jiankang Vocational University (JK201405).

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