The Role Of ErbB4 In Hepatitis And Liver Carcinoma And Its Preliminary Mechanism

Background and Objective:The liver disease is the main disease that threatens human’s life and health,with higher morbidity and mortality in our country.For example,chronic hepatisis caused by chronic liver injury can lead to liver fibrosis,or even liver carcinoma,which makes the liver lose it’s normal structure and function,affecting human’s health.So far,there is no effective threapy for hepatitis,liver fibrosis and liver carcinoma,so it is urgent to explore it’s potential mechanism of those diseases.ErbB4 is one of the receptor tyrosine kinases of the ErbB family,many ligands can activate ErbB4,and then ErbB4 forms homo- or heterodimers with itself or other ErbB members.The tyrosine kinase activity can be activated by the dimers,induces tyrosine autophosphorylation and a series of signaling pathways which may generate a variety of response,such as cell differentiation,proliferation,and migration.Many research have found that there is a dysregulated expression of ErbB4 in breast cancer,bladder cancer,prostate cancer,pancreatic cancer,kidney cancer and other tumors,suggesting that ErbB4 involves in the regulation of tumors,but the mechamism of ErbB4 in hepatic disease including liver carcinoma is not clear and needs to be further studied.Methods:In this research,we take the knockout mice as the study object,establish the relationship between ErbB4 and liver injury by establishing mouse models of chronic liver injury and liver carcinoma by drugs to explore the role of ErbB4 in the progression of hepatisis and liver carcinoma,provide reliable theoretical basis for timely treatment.Results:1.When ErbB4 is knockout in the liver,it accelerates the injury of the liver,reduces the inflammation and fibrosis of the liver induced by CCL4 in mouse.2.The expression of ErbB4 can suppress the progression of liver carcinoma.3.ErbB4 and its metabolism related genes may play a role in liver carcinoma;ErbB4 may contact with E2F1,regulating the expression of Tp53inp1 to affect the development of hepatocellular carcinoma. Conclusion:ErbB4 may reduce the susceptibility to liver inflammation and carcinogesis through interrupting the metabolism pathway or dysregulating tumor suppressor Tp53inp1.