AUTHOR=Liu Hui , Lu Wei-Li , Hong Hai-Qin , Li Meng-Jun , Ye Man-Ping , Rao Qiu-Fan , Kong Jin-Ling , Luan Shao-Hua , Huang Yan , Hu Qing-Hua , Wu Fan-Rong 

TITLE=CaM/CaMKII mediates activation and proliferation of hepatic stellate cells regulated by ASIC1a

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.996667

DOI=10.3389/fphar.2022.996667

ISSN=1663-9812

ABSTRACT=phenotypic activation of hepatic stellate cells plays a central role in the development of hepatic fibrosis, and inhibiting the proliferation and clearance of activated HSCs in the damaged liver is an
appropriate therapeutic strategy for the treatment and treatment of hepatic
fibrosis. However, the mechanism leading to the activation of hepatic stellate cells is not completely clear. Acid-sensitive ion channel 1a (ASIC1a) is a cation channel activated by extracellular acid that allows Ca2+ and Na+ to flow into the cell. It is widely involved in the occurrence and development of inflammatory diseases, suggesting that ASIC1a may play an important role in liver fibrosis. The previous study of the project team found that when the membrane channel protein ASIC1a was opened, the intracellular Ca2+ increased, the expression of CaM/CaMKⅡ in HSC was high, and HSC was activated and proliferated. Therefore, we established a SD rat model of hepatic fibrosis and induce HSC-T6 activation by stimulating ASIC1a with acid in vitro. In vivo, CCl4 was used to induce liver fibrosis in rats, and then different doses of KN93(0.5, 1, 2mg/kg/d) and colchicine(0.1mg/kg/d) were given. Eight weeks later, the activities of ALT andAST in serum, HE and Masson staining in liver tissue, immunohistochemistry analysis were detected in SD rats. The expressions of ASIC1a, α-SMA, Collagen-1, CaM andCaMKⅡ were detected. Starting with the intracellular signal CaM/CaMKⅡ of HSC, the internal relationship and essence of various factors such as Ca2+, CaM/CaMKII and their downstream related proteins were found, and the cellular and molecular mechanism of ASIC1a regulating the activation and proliferation of HSC was clarified, so as to provide new ideas for the prevention and treatment of liver fibrosis. To sum up, we concluded that CaM/CaMKⅡ participates in the process of ASIC1a regulating the proliferation and activation of HSC and promotes the occurrence of liver fibrosis.