Aberrant Hepatic MicroRNA Expression in Nonalcoholic Fatty Liver Disease

Autor: Yue Ying Feng, Xiao Qin Xu, Chen Bo Ji, Chun Mei Shi, Xi Rong Guo, Jun Fen Fu
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: Cellular Physiology and Biochemistry, Vol 34, Iss 6, Pp 1983-1997 (2014)
Druh dokumentu: article
ISSN: 1015-8987
1421-9778
DOI: 10.1159/000366394
Popis: Background/Aim: Emerging evidence suggests that microRNA (miRNA) mediated gene regulation influences the maintenance of metabolic homeostasis, particularly the states of obesity and insulin resistance, thereby providing a potential link between miRNAs and nonalcoholic fatty liver disease (NAFLD). Methods: Sprague-Dawley rats fed a high-fat diet (HFD) were used to establish a rat model of NAFLD. The miRNA expression profile of liver tissues was evaluated using Illumina HiSeq deep sequencing. Selected miRNAs were then validated by real-time PCR at both 4- and 12-week time points. Furthermore, the expression levels of these miRNAs were assessed in HepG2 cells and human hepatocytes treated with free fatty acids (FFAs) and proinflammatory factors (tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Results: Our results showed that consumption of a HFD for 4 weeks caused simple steatosis, which progressed to steatohepatitis at 12 weeks. miRNA deep sequencing analysis identified 44 known up-regulated miRNAs (fold change >1.5) and 12 down-regulated miRNAs (fold change in vitro and vivo. Interestingly, the expression levels of these six miRNAs were increased in HepG2 cells and human hepatocytes after treatment with FFAs and proinflammatory factors. Conclusion: These findings suggest a critical role for miRNAs in the pathogenesis of NAFLD.
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