Involvement of microRNA-146a in diabetic peripheral neuropathy through the regulation of inflammation

Abstract

PurposeRecent evidence has shown the involvement of inflammation in the development of diabetic peripheral neuropathy (DPN). MicroRNA-146a (miR-146a) is closely involved in the inflammatory response. However, the role of miR-146a in the inflammatory reaction in DPN has not been clarified. This study was designed to explore the role of miR-146a in the regulation of inflammatory responses in DPN.MethodsRats were randomly divided into three groups (n=6 per group): control group, type 2 diabetes mellitus (T2DM) group and DPN group. T2DM and DPN rats were intraperitoneally injected with streptozotocin. Sciatic nerve conduction velocity (NCV) was determined at the 6th week and the 12th week in each group. The expression of microRNAs was detected by quantitative real-time polymerase chain reaction in three sciatic nerves for each group of rats. Expression of inflammatory cytokines in nerve tissues and plasma was measured by Western blot and Bio-Plex Pro™ assays.ResultsThe NCV and expression levels of miR-146a in the DPN group were significantly decreased (P<0.01) compared to the other two groups. Expression of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the DPN group was significantly increased compared with the control and T2DM groups (P<0.01). Pearson’s correlation analysis showed that the expression level of miR-146a was negatively correlated with the levels of IL-1β, TNF-α and NF-κB.ConclusionmiR-146a is involved in the pathogenesis of DPN, and its expression level is closely related to the inflammatory responses that aggravate sciatic nerve injuries.

Emerging Roles of microRNAs as Biomarkers and Therapeutic Targets for Diabetic Neuropathy

“…Zhang et al, reported that miR-25 decreased reactive oxygen species content in diabetic peripheral nerves by activating NADPH oxidase and upregulating Advanced glycation endproduct (AGE)-RAGE interaction (50), In a diabetic state, reduced miR-146a expression was observed in serum, leukocytes, retina, heart, and PNS (65)(66)(67). MiR-146a was also reported to be involved in DN progression (64,68). Our recent experimental study adds substantially to this body of evidence (63).…”

Cerium- and Iron-Oxide-Based Nanozymes in Tissue Engineering and Regenerative Medicine

“…Within this study, the CO-NPs were conjugated to microRNA with the goal to enhance the inflammatory response [159]. MiR-146a was chosen due to its reported ability to target adapter molecules of the NF-κB pathway, resulting in increased IL-6 and IL-8 gene expression [160][161][162]. The authors could show that CO-NP or miR146a treatment alone did not have an effect on the healing rate compared to the saline control in both mouse and pig diabetic wound-healing models.…”

MicroRNA Mediated Regulation of Schwann Cell Migration and Proliferation in Peripheral Nerve Injury

“…miRNA-146a plays a role in diabetic peripheral neuropathy [ 55 , 56 ]. miRNA-146a in sciatic nerve tissue was attenuated in mice with type 2 diabetes and miRNA-146a levels in plasma and sciatic nerve tissue were enhanced following administration of miRNA-146a mimics in diabetic mice.…”