Liver-specific microRNA-185 knockout promotes cholesterol dysregulation in mice
作者机构：Harold Hamm Diabetes CenterDepartment of PhysiologyUniversity of Oklahoma Health Sciences CenterOklahoma CityOKUSA
出 版 物：《Liver Research》 (肝脏研究（英文）)
年 卷 期：2021年第5卷第4期
页 面：232-238页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：This study was supported by the USA National Institutes of Health(NIH)grant 1R01 DK117965-01A1(T.Li)
主 题：MicroRNA(miRNA) MicroRNA-185(miR-185) Cholesterol Fatty liver
摘 要：Background:The liver plays a key role in regulating whole body cholesterol *** cholesterol accumulation causes liver injury in fatty liver disease and hypercholesterolemia increases the risk of cardiovascular ***(miRNAs,miRs)have been shown to regulate various pathways in cholesterol ***,miR-185 has been shown to regulate sterol regulatory element-binding protein 2(SREBP2)and low-density lipoprotein receptor(LDLR)to modulate cholesterol syn-thesis and *** and methods:The role of miR-185 in regulating diet-induced metabolic disorders were studied in liver-specific miRNA-185 knockout(L-miR-185 KO)***:L-miR-185 KO mice developed worsened hepatic steatosis upon high-fat high-cholesterol Western diet feeding with accumulation of triglyceride and cholesterol in the *** addition,L-miR-185 KO mice developed hypercholesterolemia upon Western diet *** expression analysis showed that L-miR-185 KO mice did not show increased hepatic mRNA expression of SREBP2 or its targets LDLR and HMG-CoA reductase(HMGCR).Although expression of miR-185 mimic inhibited the mRNA of SREBP2,HMGCR and LDLR in HepG2 cells,miR-185 inhibitor did not increase the mRNA of SREBP2,HMGCR or LDLR in HepG2 ***:In conclusion,we reported that L-miR-185 KO mice were more sensitive to Western diet induced hepatic steatosis and *** molecular mechanisms underlying these metabolic changes remain to be investigated in future studies.
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