Exploring the Role of Micro Rnas as Key Regulators of Diabetic Nephropathy Induced Cardiovascular Diseases

Abstract

Diabetic nephropathy (DN) refers to the impairment of kidney function that occurs in patients with type 1 and type 2 diabetes mellitus. Diabetic Patients with kidney disease have an exceptionally high risk of developing cardiovascular complications. The hyperglycemic condition leads to the generation of oxidative stress, upregulation of the renin-angiotensin-aldosterone system, inflammation, initiation of the immune system, arterial stiffening, abnormal endothelial dysfunction, and nitric oxide metabolism. These changes lead to the dysregulation of various signaling cascades that ultimately causes cardiovascular diseases in a patient with diabetic nephropathy. There is a need to develop reliable strategies to prevent diabetic nephropathy before the progression of CVD. MicroRNAs are short non-coding nucleotide sequences that modulate gene expression through mRNA degradation or translational repression. We have accessed the gene target registry (GTR) for finding clinically tested genes involved in diabetic nephropathy-linked cardiovascular diseases. Bioinformatics tools including NCBI, miRanda, TargetScan, miRBase, and TarBase were used to identify different miRNAs targeting these genes. From the clinical data, we have identified that many genes expression is dysregulated which can be the direct target of miRNAs that targets them by binding at 8-mers sites. PPARG (miR-130-3p, miR-301a-3p, miR-451-3p), IL6 (miR-149-5p, miR-760), TLR4 (miR-140-5p), FTO (miR-150-5p), VDR (miR-4319, miR-125b-5p, miR-125a-5p), BDNF (miR-10b-5p, miR-10a-5p), MTHFR (miR-22-3p), VEGFA (miR-205-5p), and EDN1 (miR-1-3p, miR-206, miR-613). Conclusively, we predicted that different miRNAs targeting the genes involved in DN-linked cardiovascular diseases may pave a better path towards a miRNA-based therapeutic and diagnostic intervention for treating diabetic nephropathy-linked cardiovascular diseases.