Apelin promotes hepatic fibrosis through ERK signaling in LX-2 cells
Apelin promotes hepatic fibrosis through ERK signaling in LX-2 cells
复制标题
Apelin 通过 LX-2 细胞中的 ERK 信号传导促进肝纤维化
DOI：
10.1007/s11010-019-03581-0
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发表时间：
2019-10-01
影响因子：
4.3
通讯作者：
Lv, Xinrui
中科院分区：
文献类型：
--
作者：
Wang, Ying;Song, Jiayi;Lv, Xinrui
Apelin参与心血管功能、代谢疾病和体内平衡紊乱。然而，在肝脏疾病，特别是肝纤维化中的生物学功能仍在研究中。本研究旨在探讨apelin在非酒精性脂肪性肝病（NAFLD）中的表达，以及apelin通过ERK信号通路促进肝星状LX-2细胞肝纤维化的机制。结果表明，HFC使小鼠血清中ALT和AST水平升高。组织学染色显示HFC小鼠肝细胞脂肪变性和球囊变性严重，纤维生成表现为细胞周围胶原沉积增加和中央（小叶）周围胶原沉积增加。免疫化学和qRT-PCR结果显示，与对照组相比，apelin和profibrosis基因的表达较高。体外实验表明，apelin-13上调LX-2细胞I型胶原（collagen-I）和α -平滑肌肌动蛋白（alpha-SMA）的转录和翻译水平。免疫荧光染色、qRT-PCR和Western blot结果显示，过表达apelin显著增加了α - sma和cyclinD1的表达。apelin-13处理的LX-2细胞显示pERK1/2的表达呈时间依赖性增加，而PD98059预处理的LX-2细胞消除了apelin诱导的α - sma和cyclinD1的表达。此外，体内和体外实验表明，apelin在促进肝纤维化中起关键作用，其潜在机制可能归因于apelin通过ERK信号通路表达促纤维化基因。
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 alpha-smooth muscle actin (alpha-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 alpha-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 alpha-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.