MicroRNAs: new biomarkers and promising therapeutic targets for diabetic kidney disease

Abstract

Diabetic kidney disease (DKD) is a chronic complication of diabetes mellitus associated with significant morbidity and mortality regarded as a global health issue. MicroRNAs - small RNA molecules responsible for the post-transcriptional regulation of gene expression by degradation of messenger RNA or translational repression of protein synthesis - rank among the factors linked to the development and progression of DKD. This study aimed to offer a narrative review on investigations around the use of microRNAs in the diagnosis, monitoring, and treatment of DKD. Various microRNAs are involved in the pathogenesis of DKD, while others have a role in nephroprotection and thus serve as promising therapeutic targets for DKD. Serum and urine microRNAs levels have also been considered in the early diagnosis and monitoring of individuals with DKD, since increases in albuminuria, decreases in the glomerular filtration rate, and progression of DKD have been linked to changes in the levels of some microRNAs.

Potential role of ACE2-related microRNAs in COVID-19-associated nephropathy

“…They block the target genes by binding to the 3′UTR during transcription, repressing the messenger RNA and promoting their degradation by cleavage [ [81] , [82] , [83] ]. More than 2000 miRNAs have been identified in humans, one miRNA targets several genes, while multiple miRNAs regulate one gene [ [83] , [84] , [85] , [86] ]. The miRNAs regulate about 60% of the human protein-coding genes, indicating their significant role in expression [ 82 , 84 , 85 , 87 ].…”

“…Chung et al showed that miR-192 was highly upregulated in progressive kidney fibrosis in a mouse and rat model of kidney disease [ 101 ]. Lorenzen et al reported that miR- 210 was a reliable marker of acute rejection and a predictor of long-term graft function ([ 79 ], while the human CKD and kidney transplant study by Ulbing et al showed significant changes in the levels of systemic miR-223-3p and miR-93-5p based on CKD stages, as well as inflammation and other bone parameters [ 86 , 102 , 114 ]. Zhang C et al reported that the levels of urinary miR-196a significantly increased in focal-segmental glomerulosclerosis (FSGS) during massive proteinuria, compared with those in complete remission state.…”

“…Wang et al showed that stable miR-10 and miR-30d are present in human and animal (Male C57BL/6J mice) urine, while the elevation of urinary miR-10a and miR-30d levels serve as a novel biomarker for kidney injury [ 116 ]. Furthermore, miR-93 modulates the expression of VEGF and its downstream, which is crucial in DKD pathogenesis [ 86 , 102 , 117 ]. The high glucose concentration led to the overexpression of miR-377 in human mesangial cells.…”

“…Moreover, Wang Q et al reported that miR-377 is associated with an increased expression of protein and fibronectin in a DKD mouse model [ 118 ]. Ma J et al reported that miR-93 overexpression prevented TGF-β1-stimulated EMT and kidney fibrogenesis via modulation of Orai1 expression [ 86 , 100 , 102 ]. Furthermore, Phua YL et Al.…”

Inhibition of Angiotensin-Converting Enzyme Ameliorates Renal Fibrosis by Mitigating DPP-4 Level and Restoring Antifibrotic MicroRNAs

“…The actions and synthesis of microRNAs are tightly regulated; their expression level gets altered in the disease condition including in diabetes and diabetic nephropathy [21][22][23][24][25][26]. MiR-let-7 family members were involved in the antifibrotic mechanism of AcSDKP [9] whereas, miR-29 family members were implicated in the antifibrotic mechanism of linagliptin (DPP-4 inhibitor) [11].…”