MiR-30e-UCP2 pathway regulates alcoholic hepatitis progress by influencing ATP and hydrogen peroxide expression
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Xi Jin1, Mo-Sang Yu1,*, Yue Huang1, Zun Xiang1 and Yi-Peng Chen1
1Department of Gastroenterology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
*This author have contributed equally as the first author
Yi-Peng Chen, email: [email protected]
Keywords: miR-30e, UCP2, ALD, alcoholic hepatitis
Received: May 10, 2017 Accepted: June 16, 2017 Published: July 31, 2017
To investigate the expression of miR-30e-UCP2 pathway in different stages of alcoholic liver disease (ALD) and its capacity and mechanism in regulating alcoholic hepatitis (AH) progress. C57BL/6 mice were fed with Lieber-DeCaril (LD) diet for 4 and 12 weeks to establish models of alcoholic fat infiltration (AFI) and AH. Based on AFI feeding, the alcoholic hepatic fibrosis (AHF) was set up with additional 4 weeks 5% carbon tetrachloride intra-abdominal injection twice per week. Serum lipid and inflammation related makers were detected while H-E staining for hepatic steatosis/ inflammation and Sirius staining for hepatic fibrosis were conducted. The apoptosis degree was tested by TUNEL plot while the hydrogen peroxide (H2O2) and ATP levels were tested by colorimetric method. MiR-30e and UCP2 over-expression were carried out by synthesizing miR-30e mimic and inserting UCP2 sequence into pCDNA3.1 plasmid. Different stages of ALD were established as indicated by increased serum TG, Tch, ALT, AST, apoptosis degree and hyaluronic acid levels as well as the typical lipid deposition, inflammatory cell infiltration and fibrosis formation in AFI, AH and AHF stages. A stepwise decreased miR-30e and increased UCP2 level was identified from AFI to AHF (p<0.05). MiR-30e over-expression significantly decreased UCP2 level. After successful miR-30e over-expression in AH, its inflammation level was decreased, followed by significantly increased ATP and H2O2 levels. Therefore, MiR-30e-UCP2 pathway participates in different stages of ALD and its therapeutic effect on AH may be through influencing oxidative stress and energy metabolism.
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