Activin A-Mediated Mouse Liver Injury Induced By Concanavalin A

Activin is a member of the transforming growth factor-beta (TGF-β) superfamily as growth and differentiation factors, not only can regulate secretion of follicle-stimulating hormone (FSH) and follistatin (FS) from anterior pituitary, but also can serve as an important regulator in the process of embryo formation, nerve differentiation, hematogenous cells proliferation, tissue repair and inflammation recovery. Activin contains three forms, activin A (βAβA), activin B (βBβB) and activin AB (βAβB). Activin A not only has the strongest effect, but also close related with liver disease. It is reported that activin can cause liver fibrosis, and the inducer of liver fibrosis, TGF-β, can also depend on the effect of endogenetic activin partially.We analyzed the effect of Activin A on mouse liver fibrosis in vivo by ActRIP 2 overexpression and gene silence using liver injury model mouse. We explored the mechanism of Activin A mediating liver damage by inject Activin A in vitro and block Activin A.The biological signification of Activin A in the process of mouse liver injury induced by Con AExperimental animal model is useful to explore the mechanism of various diseases and drug screenings. Liver injure experiment animal modle induced by Con A is wildly used in human immunological liver damage and liver fibrosis research. We obtained the model of human liver injury by injecting Con A (10mg/kg) into mouse C57BL/6 for 4 weeks and observed the interrelated changes at 24h, 72h, 120h, 168h after the last injection. The results showed that mouse liver injury is the most serious at 72h and by the time going on, the pathology injure having been less serious and going on recovered. It can be relieved depending on time by serum enzymological and pathological analysis. However, Activin A expression keeped high level all the time. The above data suggested that Activin A may be associated with the development of liver injury induced by Con A.The effects of Activin A declination on mouse liver injury induced by ConAWe injected Activin A antibody, Activin A special combine protein Follistatin andⅡA recepter of Activin A into mouse C57BL/6 via tail vein after Con A stimulation for 6 hour, and to examine the variety of serum enzymological and pathological injure degree. The results showed that both serum ALT and AST increased, and all the liver indexes in Activin A blocking group are lighter than the group stimulated by Con A alone, with p< 0.01, which was coincident with the result by pathological slice examine. The hepatocytes were varicose, cytoplast showed balloon-like changes after dye, and the cells were cracked and necrotic. Whereas the indexes such as serum enzymology changes, liver changes, pathological changes were all close to normal in Activin A antibody group, which suggested that Activin A expression changes can influence on the process of liver pathological injury. It may be that Activin A paly an improtant role on hepatocyte death, ECM secretion increase and so on in liver tissue. Blocking Activin A can inhibit the function of inducing inflamming of Con A to aggravate liver pathological damage. Thus, activin A may has effects on the development of liver fibrosis and block it's signal transduction in liver to control liver disease.In conclusion, Activin A is a cell factor that highly expresses during the prosess of liver damage, and could induce liver injure, it may serve as an effective therapeutic target which can inhibit activin ontogenetic activity in liver.