CircScd1 Promotes Fatty Liver Disease via the Janus Kinase 2/Signal Transducer and Activator of Transcription 5 Pathway
- 103 Downloads
Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in affluent countries. Recent studies have reported that circular RNAs (circRNAs) are important regulators of hepatic steatosis. However, the role and mechanism of circRNA in NAFLD are poorly understood.
This study is to reveal the role and mechanism of circRNA in NAFLD.
Through NAFLD-related circRNA microarrays, we used real-time quantitative reverse transcription-polymerase chain reaction to screen circScd1 levels in control and test groups of mice fed a high-fat diet. RNA interference and over-expression plasmid vectors were used to manipulate the expression of circScd1, and the biological effects were evaluated by oil red staining, triglyceride detection, and western blot analysis.
CircScd1 expression was significantly lower in NAFLD tissues than in control tissues. Moreover, over-expression of circScd1 significantly inhibited the formation of lipid droplets. Western blot analyses showed that the protein levels of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) were significantly increased. However, knockdown of circScd1 significantly promoted the degree of hepatocellular lipidosis and reduced the expression levels of JAK2 and STAT5.
Aberrant expression of circScd1 affects the extent of hepatocellular lipidosis in NAFLD and promotes fatty liver disease via the JAK2/STAT5 pathway.
KeywordsCircScd1 Nonalcoholic fatty liver disease Steatosis Janus kinase 2 Signal transducer and activator of transcription 5
Nonalcoholic fatty liver disease
Janus kinase 2
Signal transducer and activator of transcription 5
Fed with high-fat diet
Dulbecco’s modified Eagle medium
Fetal bovine serum
Bovine serum albumin
Real-time quantitative reverse transcription-polymerase chain reaction
Small interfering RNA
This work was supported by the Zhejiang Provincial Natural Science Foundation of China (Nos. LQ18H160015 to P.L. and LY13H030012 to L.X.), the National Natural Science Foundation of China (No. 81300703 to L.X.), and the Ningbo Natural Science Foundation of China (Nos. 2015A610183 and 2015A610178).
Compliance with ethical standards
Conflict of interest
- 6.Chalasani N, Younossi Z, Lavine E, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Am J Gastroenterol. 2012;107:811–826.CrossRefGoogle Scholar
- 18.Xu L, Xu C, Yu Z, et al. Association between serum growth hormone levels and nonalcoholic fatty liver disease: a cross-sectional study. PLoS ONE. 2012;46:504–513.Google Scholar
- 21.Shi SY, Martin RG, Duncan RE, et al. Hepatocyte-specific deletion of Janus kinase 2 (JAK2) protects against diet-induced steatohepatitis and glucose intolerance. J Biol Chem. 2012;287:0277–10288.Google Scholar
- 25.Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55:2005–2023.CrossRefGoogle Scholar