Cheng Xiao-Yu, Liu Jun-Da, Lu Xin-Yi, Yan Xing, Huang Cheng, Meng Xiao-Ming, Li Jun
The Key Laboratory of Major Autoimmune Diseases, The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Anhui Institute of Innovative Drugs, Institute for Liver Diseases, School of Pharmacy, Anhui Medical University, Hefei, China.
Front Pharmacol. 2018 Apr 4;9:275. doi: 10.3389/fphar.2018.00275. eCollection 2018.
Alcoholic liver disease (ALD) is a global liver disease which characterized by liver inflammation, fatty liver, alcoholic hepatitis, or liver cirrhosis. Alcohol abuse is one of the main reasons for liver disease. Alcoholic fatty liver (AFL) disease is the early stage of ALD and associated with the excessive lipids accumulation in hepatocytes as well as oxidative stress. MicroRNA-203 (miR-203) is known to suppress the proliferation and metastasis of hepatocellular carcinoma, but the role in the progression of alcoholic liver disease is not clear and is warranted for further investigation. In the present study, we have found the expression of miR-203 is down-regulated in Gao-Binge alcoholic mice model and ethanol-induced AML-12 cell lines . Furthermore, over-expression of miR-203 decrease the lipids accumulation in liver and ethanol-induced AML-12 cells. Mechanistically, we identified that Lipin1 is a key regulator of hepatic lipid metabolism, and acts as a downstream target for miR-203. In summary, our results suggested that over-expression of miR-203 inhibited the liver lipids accumulation and the progression of AFL by targeting Lipin1.
酒精性肝病(ALD)是一种全球性的肝脏疾病,其特征为肝脏炎症、脂肪肝、酒精性肝炎或肝硬化。酗酒是肝病的主要原因之一。酒精性脂肪肝(AFL)疾病是ALD的早期阶段,与肝细胞内脂质过度积累以及氧化应激相关。已知微小RNA-203(miR-203)可抑制肝细胞癌的增殖和转移,但其在酒精性肝病进展中的作用尚不清楚,有待进一步研究。在本研究中,我们发现miR-203在高剂量狂饮酒精小鼠模型和乙醇诱导的AML-12细胞系中表达下调。此外,miR-203的过表达减少了肝脏和乙醇诱导的AML-12细胞中的脂质积累。机制上,我们确定Lipin1是肝脏脂质代谢的关键调节因子,并且是miR-203的下游靶点。总之,我们的结果表明,miR-203的过表达通过靶向Lipin1抑制肝脏脂质积累和AFL的进展。