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Apelin promotes hepatic fibrosis through ERK signaling in LX-2 cells.


ABSTRACT: Apelin participates in cardiovascular functions, metabolic disease, and homeostasis disorder. However, the biological function of apelin in liver diseases, especially liver fibrosis is still under investigation. The present study aimed to investigate the expression of apelin in nonalcoholic fatty liver disease (NAFLD) and the mechanism of apelin promoting hepatic fibrosis through ERK signaling in hepatic stellate LX-2 cells. The results showed that the ALT and AST levels in serum were increased in the mice fed HFC. The histological staining revealed that hepatocellular steatosis and ballooning degeneration was severe, and fibrogenesis appeared as increased pericellular collagen deposition along with pericentral (lobular) collagen deposition in the mice fed HFC. Immunochemistry and qRT-PCR results showed that the expression of apelin and profibrotic genes was higher as compared to the control group. The in vitro experiments demonstrated that apelin-13 upregulated the transcription and translation levels of collagen type I (collagen-I) and ?-smooth muscle actin (?-SMA) in LX-2 cells. The immunofluorescent staining, qRT-PCR, and Western blot results showed that the overexpression of apelin markedly increased the expression of ?-SMA and cyclinD1. The LX-2 cells treated with apelin-13 displayed an increased expression of pERK1/2 in a time-dependent manner, while the pretreatment with PD98059 abolished the apelin-induced expression of ?-SMA and cyclinD1. Furthermore, the in vivo and in vitro assays suggested a key role of apelin in promoting liver fibrosis, and the underlying mechanism might be ascribed to the apelin expression of profibrotic genes via ERK signaling pathway.

SUBMITTER: Wang Y 

PROVIDER: S-EPMC6745032 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Apelin promotes hepatic fibrosis through ERK signaling in LX-2 cells.

Wang Ying Y   Song Jiayi J   Bian Hongyan H   Bo Jiaqi J   Lv Shuangyu S   Pan Weitong W   Lv Xinrui X  

Molecular and cellular biochemistry 20190703 1-2


Apelin participates in cardiovascular functions, metabolic disease, and homeostasis disorder. However, the biological function of apelin in liver diseases, especially liver fibrosis is still under investigation. The present study aimed to investigate the expression of apelin in nonalcoholic fatty liver disease (NAFLD) and the mechanism of apelin promoting hepatic fibrosis through ERK signaling in hepatic stellate LX-2 cells. The results showed that the ALT and AST levels in serum were increased  ...[more]

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