The Identification And Function Analysis Of ANXA2 In Liver Cirrhosis Rats Induced By Carbon Tetrachloride

Objective: Liver cirrhosis represents a worldwide health problem and a major cause of mortality. It resulted from a long time or repeated effects of a or various hepatitis diseases, which developed into a chronic 、developing and diffused liver injury by the deposition of collagen and the vascular dysfunction. Although a great number of progresses has made which leads to a better understanding of liver cirrhosis, the mechanism of the liver cirrhosis is still unclear, liver transplantation is the only effective treatment for liver cirrhosis. The aim of this study is to find the key proteins involved in the development of liver cirrhosis which may function as a target for the reversion of liver cirrhosis and the management of its complications.Methods: The rat model of liver cirrhosis was successfully performed by intraperitoneal injection of 40% CCl₄ for 12 weeks. In order to find the differentially expressed proteins in liver cirrhosis, we employed iTRAQ coupled with LC-MS/MS to detect the differentially expressed proteins of the liver cirrhosis rats. Our liver samples were derived from two subgroups:（1） carbon tetrachloride induced-liver cirrhosis rats;（2） the correspondingbackground of normal control rats. We employed real-time PCR and western blotting for a further verification. Then, we selected an over expressed protein（ANXA2） in liver cirrhosis rats to study its influence on the secretion of vWF by the silencing of ANXA2 using ANXA2 siRNAs.At the same time, we detected the serum levels of vWF and ANXA2 in liver cirrhosis patients and healthy people, then we performed a correlation analysis of the serum level of ANXA2 and vWF in liver cirrhosis patients.Results: we identified totally 1892 proteins among which there was134 differentially expressed protein between the CCl₄ induced-liver cirrhosis rats and the normal control rats, including 24 up-regulated and110 down-regulated proteins. Employing real-time PCR and Western blotting, we verified the differential expressed proteins（including ANXA2,KRT8, ALDOB, GPX1）, and the results were consistent with iTRAQ. We selected ANXA2 to conduct the following study, and the results showed that the secretion of vWF reduced after the silencing of ANXA2 gene.Moreover, we found that the concentrations of ANXA2 and vWF in the serum of liver cirrhosis patients were significantly increased, which were positively related.Conclusion: in all, our study successfully constructed a rat model of liver cirrhosis. We found that ANXA2 was overexpressed in liver cirrhosis.ANXA2 may affect the occurrence and development of liver cirrhosis by affecting the secretion of vWF.