Premium
Inhibiting miR‐27a and miR‐142‐5p attenuate nonalcoholic fatty liver disease by regulating Nrf2 signaling pathway
Author(s) -
Teimouri Maryam,
Hosseini Hossein,
Shabani Maryam,
Koushki Mehdi,
Noorbakhsh Farshid,
Meshkani Reza
Publication year - 2020
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.2221
Subject(s) - nonalcoholic fatty liver disease , microrna , in vivo , downregulation and upregulation , western blot , transfection , in vitro , chemistry , biology , fatty liver , endocrinology , medicine , gene , biochemistry , disease , genetics
Summary The gene Nrf2 (nuclear factor‐erythroid 2‐related factor 2) is the most important regulator of the cellular antioxidant system and its dysregulation has a role in the etiology of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the association between Nrf2 targeted miRNAs (miR‐27a, miR‐142‐5p, miR‐153, and miR‐128) with lipid accumulation in vitro and in vivo models of NAFLD. We used two in vivo and in vitro models of NAFLD. The expression of the genes and miRNAs was assessed by real‐time PCR and the protein level was evaluated using western blot. To investigate the potential role of miRNAs in NAFLD, the inhibitors or mimics of the miR‐27a and miR‐142‐5p were transfected into HepG2 cells. The mRNA and protein levels of Nrf2 were significantly decreased in the liver of high fat diet‐fed mice as well as in HepG2 cells treated with high glucose (HG). Reduced expression of Nrf2 was associated with increased expression levels of miR‐27a and miR‐142‐5p in both models of NAFLD. HG‐induced triglyceride accumulation was attenuated by inhibition of miR‐27a or miR‐142‐5p in HepG2 cells. Overexpression of miR‐27a or miR‐142‐5p suppressed the expression of Nrf2 and its downstream antioxidant genes and increased production of reactive oxygen species, whereas inhibition of miR‐27a or miR‐142‐5p reversed these effects. In conclusion, the data of this study may suggest that miR‐27a and miR‐142‐5p are increased in NAFLD, where they suppress Nrf2 expression and contribute to the accumulation of lipids in the hepatocytes.