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.

Role of exosomes in malignant glioma: microRNAs and proteins in pathogenesis and diagnosis

“…Proteins with these lipid modifications enter the lipid rafts consisting of sphingomyelins, cholesterols and ceramides in a selective manner. The lipid rafts accumulate in the exosomal membranes [ 29 , 30 ]. Cellular exosome release has been reported to be up-regulated by HIV-1 viral infection, which immediately leads to ESCRT-independent biogenesis of exosomes.…”