Department of Gastroenterology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, Sichuan, China.
Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, Sichuan, China.
Aging (Albany NY). 2020 May 15;12(10):9066-9084. doi: 10.18632/aging.103172.
This study aimed to figure out the underlying mechanism of miR-142-5p in the non-alcoholic steatohepatitis (NASH). Bioinformatics, luciferase assay and Western blot were performed. The NASH mouse model was established through feeding a high fat diet (HFD). Relative expressions of miR-142-5p, thymic stromal lymphopoietin (, inflammatory factors were detected by qRT-PCR. The injury level of liver was assessed via measurement of serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST). H&E staining and Masson's trichrome staining examine the liver fatty degeneration and fibrosis. MiR-142-5p and TSLP were differentially expressed and JAK-STAT signaling pathway was activated in the NASH group. Luciferase assay identified that was the downstream target of miR-142-5p. Through overexpression of miR-142-5p, ALT and AST in serum were inhibited, pro-inflammatory factors, liver fatty degeneration and fibrosis in liver tissues were decreased, while anti-inflammatory factors were increased. Overexpression of and JAK-STAT signaling pathway activation could reverse the effects of miR-142-5p on NASH. Taken together, overexpression of miR-142-5p could attenuate NASH progression via inhibiting and JAK-STAT pathway. MiR-142-5p might be a novel latent target for NASH therapy.
本研究旨在探讨 miR-142-5p 在非酒精性脂肪性肝炎（NASH）中的作用机制。进行了生物信息学、荧光素酶测定和 Western blot 分析。通过给予高脂肪饮食（HFD）建立 NASH 小鼠模型。通过 qRT-PCR 检测 miR-142-5p、胸腺基质淋巴细胞生成素（TSLP）和炎症因子的相对表达水平。通过测量血清丙氨酸氨基转移酶（ALT）和血清天冬氨酸氨基转移酶（AST）评估肝损伤程度。通过 H&E 染色和 Masson 三色染色检查肝脂肪变性和纤维化。NASH 组中 miR-142-5p 和 TSLP 表达差异，JAK-STAT 信号通路激活。荧光素酶测定鉴定出是 miR-142-5p 的下游靶标。通过过表达 miR-142-5p，抑制血清中 ALT 和 AST 的升高，减少肝组织中促炎因子、肝脂肪变性和纤维化，增加抗炎因子。过表达和 JAK-STAT 信号通路的激活可以逆转 miR-142-5p 对 NASH 的作用。综上所述，过表达 miR-142-5p 可以通过抑制和 JAK-STAT 通路来减轻 NASH 的进展。miR-142-5p 可能是 NASH 治疗的新潜在靶点。
