MicroRNA-26a–interleukin (IL)-6–IL-17 axis regulates the development of non-alcoholic fatty liver disease in a murine model

Abstract

SummaryNon-alcoholic fatty liver disease (NAFLD) is a hepatic presentation of obesity and metabolic syndrome. MicroRNA 26a (Mir-26a) has been reported to play functions in cellular differentiation, cell growth, cell apoptosis and metastasis. A recent paper indicated that Mir-26a regulated insulin sensitivity and metabolism of glucose and lipids. However, the role of Mir-26a in NAFLD still needs to be investigated further. In our current study, vectors encoding pre-Mir-26a (LV-26a) and an empty lentiviral vector (LV-Con) delivered approximately 2 3 10 7 transforming units of recombinant lentivirus were injected into mice through the tail vein. LV-26a-infected mice were protected from glucose dysmetabolism and showed markedly decreased total liver weight, hepatic triglyceride deposition and serum alanine transaminase (ALT) concentration when compared with LV-Con-treated mice. LV-26a-treated mice also exhibited decreased infiltration of immune cells in the liversomething attributed to reduce infiltration of T cell receptor (TCR)-gd 1 , granulocyte-differentiation antigen-1 (Gr-1) 1 cells and CD11b 1 cells. Next, we found that Mir-26a inhibited the expression of interleukin (IL)217 and IL-6 in vivo and in vitro. Furthermore, the decreased expression of IL-17 in the liver tissue induced by Mir-26a was abrogated completely by IL-6 overexpression. The decreased total liver weight, hepatic triglyceride deposition and serum ALT concentration induced by Mir-26a was also abrogated completely by IL-6 over-expression. In conclusion, the Mir-26a-IL-6-IL-17 axis regulates the development of NAFLD in a murine model.

miR‐26a Potentially Contributes to the Regulation of Fatty Acid and Sterol Metabolism In Vitro Human HepG2 Cell Model of Nonalcoholic Fatty Liver Disease

“…Moreover, our results determined that miR-26a overexpression downregulated the mRNA expression levels of inflammatory marker IL-6 and fibrogenic markers TGFβ1 and TGFβ2. In an agreement, former studies have shown that miR-26a inhibited the production of some inflammatory mediators such as IL-6 and IL-17 , while it attenuated fibrogenesis under both in vitro and in vivo conditions [ 45 , 53 ].…”

“…In tune, this study showed the miR-26a overexpression significantly decreased MDA level and increased TAC after HepG2 cell treatment with FFA. This effect of miR-26a on lipid peroxidation was previously addressed [ 45 ].…”

The role of infiltrating immune cells in dysfunctional adipose tissue

“…It appears that IL-6 regulates recruitment of these cells and IL-17 production in the liver that promotes ectopic fat. 194 This is in part regulated by decreased microRNAs (miR) such as miR26a, providing a link to cardiac injury. 195 Similar regulatory properties have been attributed to other miRs expressed in the AT and cardiovascular system.…”

An Integrative miRNA-mRNA Expression Analysis Reveals Striking Transcriptomic Similarities between Severe Equine Asthma and Specific Asthma Endotypes in Humans

“…Several differentially expressed miRNAs detected in the lungs of horses in exacerbation compared to controls are linked with the positive regulation of the Th17 pathway. Indeed, downregulated miR-26a leads to increased expression of IL-17 and IL-6 [ 54 ] and affects Th17/Treg balance towards Th17 cells [ 55 ]. Additionally, miR-31 drives Th17 cell differentiation through targeting IL-25, while suppressing Treg differentiation through FOXP3 [ 56 ].…”