MicroRNA 21 Emerging Role in Diabetic Complications: A Critical Update

Abstract

Background: Diabetes Mellitus is a multifactorial disease encompassing various pathogenic pathways. To avoid morbidity and mortality related to diabetic complications, early detection of disease complications as well as targeted therapeutic strategies are essential.

Introduction: MicroRNAs (miRs) are short non-coding RNA molecules that regulate eukaryotic posttranscriptional gene expression. MicroRNA-21 has diverse gene regulatory functions and plays a significant role in various complications of Type 2 diabetes mellitus (T2DM).

Methods: The study included electronic database searches on Pubmed, Embase, and Web of Science with the search items MicroRNA21 and each of the diabetic complications. The search was carried out up to November, 2019.

Results: MicroRNA-21 modulates diabetic cardiomyopathy by affecting vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. At the renal tubules, miR-21 can regulate the mesangial expansion, interstitial fibrosis, macrophage infiltration, podocyte loss, albuminuria and fibrotic and inflammatory gene expression related to diabetic nephropathy. Overexpression of miR-21 has been seen to play a pivotal role in the pathogenesis of diabetic retinopathy by contributing to diabetes-induced endothelial dysfunction as well as low-grade inflammation.

Conclusion: Considering the raised levels of miR-21 in various diabetic complications, it may prove to be a candidate biomarker for diabetic complications. Further, miR-21 antagonists have shown great potential in the treatment of diabetic cardiomyopathy, diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy related complications in the future. The current review is the first of its kind encompassing the roles miR-21 plays in various diabetic complications, with a critical discussion of its future potential role as a biomarker and therapeutic target.

Keywords: MicroRNA-21; Type 2 diabetes mellitus; diabetic neuropathy; diabetic cardiomyopathy; diabetic nephropathy; diabetic retinopathy.