Chu Kaifeng, Gu Jie
Department of Hepatology, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, P.R. China.
Department of Gastroenterology, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, P.R. China.
Immunopharmacol Immunotoxicol. 2022 Dec;44(6):993-1003. doi: 10.1080/08923973.2022.2102988. Epub 2022 Jul 28.
As a metabolic-associated disease, nonalcoholic fatty liver disease (NAFLD) development is tightly linked to lipid accumulation, inflammatory response, and fibrosis. Our study was intended to expound the role of microRNA (miR)-103a-3p in the pathogenesis of NAFLD.
First, potentially relevant genes in NAFLD were screened using microarray analysis. The expression of lipid metabolism-related, inflammatory, and liver fibrosis indicators in the serum of patients with NAFLD was analyzed. We established a NAFLD mouse model and analyzed the serum level of lipid metabolism- and inflammation-related factors and fibrosis in the liver tissues of NAFLD mice. The targeting relationship between miR-103a-3p and HBP1 was examined by dual-luciferase reporter gene assay, RT-qPCR, and Western blot. Finally, the simultaneous effects of miR-103a-3p and HBP1 knockdown on lipid metabolism, inflammatory response, and liver fibrosis in NAFLD mice were analyzed by rescue experiments.
MiR-103a-3p was upregulated in the serum of NAFLD patients and liver tissues of NAFLD mice, with increased lipid accumulation, inflammation, and liver fibrosis. HBP1 was reduced in liver tissues of NAFLD mice, and miR-103a-3p bound to and negatively regulated HBP1. Inhibition of miR-103a-3p or promotion of HBP1 improved liver function, decreased lipid accumulation, suppressed inflammatory response, and reduced liver fibrosis in NAFLD mice. Moreover, sh-HBP1 partially reversed the effect of miR-103a-3p inhibitor on NAFLD mice, leading to increased lipid accumulation, elevated inflammation, and fibrosis in the liver of mice.
miR-103a-3p inhibits the expression of HBP1, thus suppressing lipid metabolism, stimulating inflammatory responses, and promoting liver fibrosis in NAFLD.
作为一种代谢相关疾病，非酒精性脂肪性肝病（NAFLD）的发展与脂质积累、炎症反应和纤维化密切相关。我们的研究旨在阐明微小RNA（miR）-103a-3p在NAFLD发病机制中的作用。
首先，使用微阵列分析筛选NAFLD中潜在相关基因。分析NAFLD患者血清中脂质代谢相关、炎症和肝纤维化指标的表达。我们建立了NAFLD小鼠模型，并分析了NAFLD小鼠血清中脂质代谢和炎症相关因子水平以及肝脏组织中的纤维化情况。通过双荧光素酶报告基因检测、RT-qPCR和蛋白质免疫印迹法检测miR-103a-3p与HBP1之间的靶向关系。最后，通过挽救实验分析miR-103a-3p和HBP1基因敲低对NAFLD小鼠脂质代谢、炎症反应和肝纤维化的联合影响。
miR-103a-3p在NAFLD患者血清和NAFLD小鼠肝脏组织中上调，脂质积累、炎症和肝纤维化增加。NAFLD小鼠肝脏组织中HBP1减少，且miR-103a-3p与HBP1结合并对其进行负调控。抑制miR-103a-3p或促进HBP1可改善NAFLD小鼠的肝功能，减少脂质积累，抑制炎症反应，并减轻肝纤维化。此外，sh-HBP1部分逆转了miR-103a-3p抑制剂对NAFLD小鼠的作用，导致小鼠肝脏脂质积累增加、炎症和纤维化加剧。
miR-103a-3p抑制HBP1的表达，从而抑制NAFLD中的脂质代谢，刺激炎症反应并促进肝纤维化。
