Overexpression of microRNA-216a-3p Accelerates the Inflammatory Response in Cardiomyocytes in Type 2 Diabetes Mellitus by Targeting IFN-α2

• Main Authors: Xiaomeng Liu, Yusong Zhang, Hongwei Liang, Yanchao Xu
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2020-11-01
• Series: Frontiers in Endocrinology
• Subjects: microRNA-216a-3p; interferon-α2; Toll-like receptor signaling pathway; type 2 diabetes mellitus; cardiomyocytes; proliferation
• Online Access: https://www.frontiersin.org/articles/10.3389/fendo.2020.522340/full

Background: Type 2 diabetes mellitus (T2DM) is a chronic, hyperglycemia-associated, metabolic disorder. Heart disease is a major complication of T2DM. The present study aimed to explore the effects of miR-216a-3p on cardiomyocyte proliferation, apoptosis, and inflammation in T2DM through the Toll-like receptor (TLR) pathway involving interferon-α2 (IFN-α2) mediation.Methods: T2DM was induced in rats by a high-fat diet, in combination with an intraperitoneal injection of low-dose streptozotocin. ELISAs were conducted to measure inflammatory-related factors in serum. Next, isolated cardiomyocytes were used in loss- and gain-of-function experiments, followed by MTT and flow cytometry assays, conducted to evaluate cell proliferation, cell cycle, and apoptosis.Results: Our results revealed an increase in the inflammatory response in T2DM rat models, accompanied by significantly increased expression of miR-216a-3p and TLR pathway-related genes. However, a decrease in the expression of IFN-α2 was observed. Moreover, the presence of an miR-216a-3p inhibitor and si-IFN-α2 increased the expression of TLR pathway-related genes and cell apoptosis, whereas cell proliferation was significantly decreased in the cardiomyocytes.Conclusion: We found that in T2DM, miR-216a-3p inhibited the proliferation and enhanced the apoptosis of cardiomyocytes and generated an inflammatory response through activation of the TLR pathway and targeting of IFN-α2.