MicroRNA-146a: A Comprehensive Indicator of Inflammation and Oxidative Stress Status Induced in the Brain of Chronic T2DM Rats

Abstract

Objective: It was demonstrated that inflammation and oxidative stress induced by hyperglycemia were closely associated with alteration of miR-146a. Here, we investigated the role of miR-146a in mediating inflammation and oxidative stress in the brain of chronic T2DM rats.Methods: The chronic T2DM (cT2DM) models were induced by intraperitoneal administration of STZ (35 mg/kg) after being fed a high-fat, high-sugar diet for 6 weeks. H&E staining was conducted to observe the morphological impairment of the rat hippocampus. The expressions of inflammatory mediators (COX-2, TNF-α, IL-1β) and antioxidant proteins (Nrf2, HO-1) were measured by western blot. The levels of MDA and SOD were detected by the respective activity assay kit. The levels of p22phox and miR-146a were examined by quantitative real-time PCR (qRT-PCR). The expressions of IRAK1, TRAF6 and NF-κB p65 were measured by western blot and qRT-PCR. Pearson correlation analysis was performed to investigate the correlations between miR-146a and inflammatory mediators as well as oxidative stress indicators.Results: The expression of miR-146a was negatively correlated with inflammation and oxidative stress status. In the brain tissues of cT2DM rats, it was observed that the expressions of inflammatory mediators (COX-2, TNF-α, IL-1β) and oxidative stress indicators including MDA and p22phox were elevated, which were negatively correlated with the expression of miR-146a. While, the antioxidant proteins (Nrf2, HO-1, SOD) levels decreased in the brain of cT2DM rats, which were positively correlated with the miR-146a level. The expressions of NF-κB p65 and its specific modulators (IRAK1&TRAF6) were elevated in the brain of cT2DM rats, which might be inhibited by miR-146a.Conclusion: Our results implied that increased inflammation and oxidative stress status were associated with brain impairment in cT2DM rats, which were negatively correlated with miR-146a expression. Thus, miR-146a may serve as a negative comprehensive indicator of inflammation and oxidative stress status in the brain of chronic T2DM rats.

Oxidative Stress-Responsive MicroRNAs in Heart Injury

“…Increased inflammation and oxidative stress were associated with brain impairment in cT2DM rats, which were negatively correlated with miR-146a expression. The expressions of NF-κB p65 and its specific modulators were elevated in the brain of cT2DM rats, which might be inhibited by miR-146a [87].…”

<p>Exosomes Derived from MicroRNA-146a-5p-Enriched Bone Marrow Mesenchymal Stem Cells Alleviate Intracerebral Hemorrhage by Inhibiting Neuronal Apoptosis and Microglial M1 Polarization</p>

“…Many studies have shown that miR-146a protects against various brain impairments. [17][18][19] It is also involved in the modulation of microglia/macrophages in ischemic stroke. 20 In addition, miR-146a-5p has been reported to be down-regulated in the serum of patients with ICH 21 and to protect against ICH by repressing the TRAF6/NF-κB pathway.…”

Circulating miR‐146a and miR‐134 in predicting drug‐resistant epilepsy in patients with focal impaired awareness seizures

“…This is attributed mainly to the ability of miR‐146a to regulate the activity of proinflammatory pathways. In this regard, in vivo and in vitro studies have shown that miR‐146a inhibits neuroinflammation by directly targeting IRAK1 and TRAF6 downstream mediators of TLR and cytokine pathways 19–22 . Increased levels of miR‐146a have been detected in brain 23,24 and blood 25,26 samples of patients with epilepsy, and have been associated with chronic neuroinflammation and neuronal loss 23,27–29 .…”