Xu Wenping, Zeng Sheng, Li Min, Fan Zhiwen, Zhou Bisheng
Department of Nursing, Jiangsu Jiankang Vocational University, Nanjing, Jiangsu 210029, China.
Department of Pathophysiology, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
J Biomed Res. 2017 Sep 26;31(5):428-436. doi: 10.7555/JBR.30.20160046.
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.
肝损伤代表了一系列病理生理过程，涉及肝细胞、巨噬细胞和肝星状细胞之间复杂的相互作用。这些细胞间相互作用导致肝损伤和纤维化的机制尚未完全阐明。我们在此报告，与健康对照相比，肝硬化患者肝脏中具有G结构域和FHA结构域的血管生成因子1（Aggf1）表达下调，并且在四氯化碳（CCl4）刺激下原代肝细胞中Aggf1也下调。Aggf1的过表达减弱了巨噬细胞趋化性。Aggf1与核因子κB（NF-κB）相互作用，阻止其与Ccl2基因启动子结合，并抑制肝细胞中Ccl2的转录。在从过表达Aggf1的肝细胞收集的条件培养基中培养的巨噬细胞可拮抗肝星状细胞激活。综上所述，我们的数据阐明了Aggf1在调节肝脏炎症中的新作用，并为抗肝硬化干预策略的开发提供了见解。
