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 theCcl2 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.
Highlights
The liver is home to a number of different cell types including hepatocytes, hepatic macrophages (Kupffer cells), and hepatic stellate cells (HSCs)
Primary mouse hepatocytes exposed CCl4 was able to attract more macrophages to migrate to the lower chamber when cultured together, a process blocked by Aggf1 overexpression in hepatocytes. These data suggest that Aggf1 may attenuate hepatic inflammation possibly by preventing hepatocyte-derived chemoattraction of macrophages
It has been well documented that a dynamic dialog between hepatic cells, including hepatocytes, hepatic stellate cells, and macrophages, contribute to the maintenance of liver homeostasis; disruption of this intricate balance leads to a host of liver pathologies such as cirrhosis[1]
Summary
The liver is home to a number of different cell types including hepatocytes, hepatic macrophages (Kupffer cells), and hepatic stellate cells (HSCs). Under normal conditions, these cells form dynamic communications and collectively maintain the hepatic homeostasis. Macrophages can produce large quantities of pro-fibrogenic growth factors such as TGF-β and CLC number: R657.31, Document code: A The authors reported no conflict of interests.
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