MicroRNAs in Podocyte Injury in Diabetic Nephropathy

Abstract

Diabetic nephropathy is one of the major complications of diabetes mellitus and is the leading cause of end-stage renal disease worldwide. Podocyte injury contributes to the development of diabetic nephropathy. However, the molecules that regulate podocyte injury in diabetic nephropathy have not been fully clarified. MicroRNAs (miRNAs) are small non-coding RNAs that can inhibit the translation of target messenger RNAs. Previous reports have described alteration of the expression levels of many miRNAs in cultured podocyte cells stimulated with a high glucose concentration and podocytes in rodent models of diabetic nephropathy. The associations between podocyte injury and miRNA expression levels in blood, urine, and kidney in patients with diabetic nephropathy have also been reported. Moreover, modulation of the expression of several miRNAs has been shown to have protective effects against podocyte injury in diabetic nephropathy in cultured podocyte cells in vitro and in rodent models of diabetic nephropathy in vivo. Therefore, this review focuses on miRNAs in podocyte injury in diabetic nephropathy, with regard to their potential as biomarkers and miRNA modulation as a therapeutic option.

The Pathogenesis of End-Stage Renal Disease from the Standpoint of the Theory of General Pathological Processes of Inflammation

“…The slow development of renal fibrosis up to the ESRD stage is due to a local ChLGI, without the hallmark morphological markers of classical inflammation, for example, in the case of the primary contracted kidney associated with essential hypertension [ 143 ]. In DKD, proinflammatory cell activation is accompanied by hypertrophy and damage to podocytes, their separation from the basement membrane, endotheliosis with the development of oxidative stress with hyperfiltration, and then glomerular sclerosis [ 14 , 144 , 145 , 146 ]. However, as previously mentioned, progressive ChLGI in DKD can acquire characteristic local signs of classical inflammation.…”

“…Negative dynamics of DKD is largely determined by the severity of proinflammatory stress in endotheliocytes and podocytes, including activation of the following signaling pathways: intercellular contact receptors Notch-1; membrane GTP-binding proteins; stress protein kinases MAPK (mitogen-activated protein kinase) and mTORC1 (mammalian target of rapamycin); many stress miRNAs and long non-coding (regulatory) RNAs; heat-shock proteins, especially HSP70; various proapoptotic factors; other factors of cellular stress, including chemokines, growth factors, and TGF-β1 [ 25 , 93 , 144 , 152 ]. …”

“…other factors of cellular stress, including chemokines, growth factors, and TGF-β1 [ 25 , 93 , 144 , 152 ].…”

MicroRNA Expression Profiling in Diabetic Kidney Disease

“…Previous studies have shown that the expression of many miRNAs is altered in the DKD; 16,29,30 however, the roles of miRNA-125b-5p and miRNA-181b-5p in DKD have not previously been reported. This may be because of differences in experimental methods and the clinical setting.…”

Network Pharmacology Combined with Bioinformatics to Investigate the Mechanisms and Molecular Targets of Astragalus Radix-Panax notoginseng Herb Pair on Treating Diabetic Nephropathy

“…miRNAs involve the fine-tuning of mRNA abundance via binding to the 3′ untranslated region of a target mRNA and results in translational repression. Increasing evidence suggests that the downregulation or upregulation of miRNAs is closely associated with podocyte injury, inflammation, accumulation of the extracellular matrix, fibrosis, and so on in DN, concerning their potential as biomarkers and miRNA modulation as a therapeutic option for DN [ 20 , 21 ]. Besides, some microarray data analysis studies related to DN have been performed and numerous DEGs have been identified, which may be potential biomarkers and target candidates in DN [ 22 ].…”