Abstract
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.
Highlights
Alcoholic fatty liver disease (ALD) was regarded as one of the most critical global health problems, which comprises a spectrum of injury, including simple steatosis, acute alcoholic hepatitis, fibrosis and cirrhosis [1]
MiR-30e-UCP2 pathway participates in different stages of alcoholic liver disease (ALD) and its therapeutic effect on alcoholic hepatitis (AH) may be through influencing oxidative stress and energy metabolism
The hepatic index was significantly increased in all alcoholic fat infiltration (AFI) (3.52 ±0.48), AH (4.17±0.44) and alcoholic hepatic fibrosis (AHF) (4.42 ±0.51) stages, comparing with control group(2.55±0.16)
Summary
Alcoholic fatty liver disease (ALD) was regarded as one of the most critical global health problems, which comprises a spectrum of injury, including simple steatosis, acute alcoholic hepatitis, fibrosis and cirrhosis [1]. MiRNAs profile have been applied in the diagnosis of various www.impactjournals.com/oncotarget diseases, including tumors [4] and nonalcoholic fatty liver disease that we previously reported [5, 6]. MiRNA-mRNA pathways have been reported to participate in various diseases [7], including miRNA-223-IL-6-p47 [8] and miR-181b-3p-importin-a5-TLR4 [9] pathways in ALD. Comparing with the identified huge miRNA data, the specific miRNA-mRNA pathways in ALD are still rare and worth further investigation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
