The Role Of SOCS3 In The Process Of Mouse Liver Fibrosis And Reverse On The Macrophage Polarization

In recent years,the incidence of liver disease has increased year by year,in a number of damage factors such as alcohol,viruses,chemicals,etc.,in the presence of liver will be different degree of damage,such as viral hepatitis,alcoholic hepatitis,liver fibrosis,liver cirrhosis,liver cancer and liver disease.And liver as an important metabolic organ of human body,its own organs in different degrees of damage directly affects the body's other disease development.Therefore,the study of the liver disease development and find the cure for liver diseases ways are imperative.Liver disease development mainly depends on the regulation of liver macrophages and hepatic stellate cells.Kupffer cells(KCs)are exist in the liver sinusoids gap within a class of non parenchymal cells and are settled in the liver of the inherent cells,KCs can nonspecific phagocytosis and clean up the bacteria in the blood,and exogenous foreign matter,such as antigenic substances,but also has specific immune response,antitumor immune response,endotoxin detoxification,anti-infection,adjust the action of the microcirculation and metabolism,etc.In liver different pathophysiological state,KCs can be polarized into different subtypes,namely the M1(classically activated macrophages)and M2(alternatively activated macrophages),M1 macrophages is also called the classic activated macrophages,mainly to promote the development of the inflammation,the secreted TNF-?(tumor necrosis factor alpha),IL-1 IL-1(interleukin 1),IL-6(interleukin 6)and other proinflammatory cytokines and passed under the action of inos will arginine into NO to kill pathogens;M2 macrophages,also known as the selective activation of macrophages,its main function is to restrain development of inflammation and repair effect to the organization,through the synthesis and secretion of anti-inflammatory cytokine IL-10(interleukin 10)and arginine is decomposed into polyamine Arg-1(arginase 1),to participate in the extracellular matrix synthesis and stability.Macrophages through the dynamic regulation of M1 and M2 to influence the liver pathological physiology,as a result,through the above phenomenon,to regulate the liver macrophage polarization and thus to achieve the recovery of liver disease with a research idea will be looking for new targets for the treatment of liver diseases and strategy.There have been studies have shown that SOCS3 participate in the development of liver disease,through the influence of various cytokines and signal transduction to produced negative regulation,such as immune regulation to affect inflammation factors and chemokines and to regulate the inflammatory response,will have the participation of inflammation,therefore,guess whether SOCS3 to participate in the development of liver fibrosis,in addition,another report showed that liver fibrosis can be reversed after the removal of damage factor[1],in turn,regulate the expression of SOCS3 protein through to affect the reverse process of liver fibrosis and liver macrophages extremely tumble type process so as to explore its effect on liver fibrosis.And the early stage of the research study found SOCS3 exist in the process of liver fibrosis and reverse the change of the expression,and macrophages in the liver and hepatic stellate cells expressed,but SOCS3 regulation role in liver fibrosis,especially of hepatic macrophages tumble related role has not been reported,so the lab research through regulating the expression of SOCS3 to observe the effects of type of KCs is extremely tumble and influence,and providing a new method for prevention and control of liver fibrosis.The main contents are divided into six sections,as follows:1.The expression of SOCS3 in the process of mouse liver fibrosis progression and reversedTake liver tissue,the use of immunofluorescence double dyeing and immunohistochemical method to observe the expression of SOCS3 in liver tissue.It is found that SOCS3 expressed in mice liver macrophages,and,along with the formation of the mice liver fibrosis,the expression of SOCS3 gradually increased,with the reversal of liver fibrosis in mice,the expression of SOCS3 gradually reduced.2.The phenotype change of macrophages in the process of liver fibrosis in mice and reverseIn different periods in situ perfusion technique to extract liver macrophages in mice,using flow cytometry technique to study on classification of hepatic macrophages.The results showed that: with the formation of liver fibrosis in.mice,CD86 labeled M1 macrophages expression gradually increased,with the reversal of liver fibrosis in mice,CD206 tag type M2 macrophages gradually increased.3.The expression of SOCS3 in RAW264.7 cells by stimulating factorIn vitro,RAW264.7 cells by LPS and IFN-? stimulate the formation of M1,IL-4 stimulus forming type M2,observation of SOCS3 expression in different classification.It is found that SOCS3 relative to M2,expressed in M1 volume increased significantly.4.The interfere expression of SOCS3 resulted of changing of RAW264.7 cells polarizationLipofectamineTM2000 transfection SOCS3 – siRNA into RAW264.7 cells,can make the LPS and IFN-? stimulate the formation of M1 expression was significantly increased,turn Lipofectamine TM2000 LV3-SOCS3-mus-1225 into RAW264.7 cells,can make the IL-4 stimulus forming type M2 expression increased significantly.