MicroRNAs in the Progress of Diabetic Nephropathy: A Systematic Review and Meta-Analysis

Abstract

Background. We conducted a systematic review and meta-analysis of existing literature to evaluate the different outcomes of microRNAs (miRNAs) in diabetic nephropathy (DN), including urinary albumin excretion rates, urinary albumin creatinine rates, glomerular filtration rate, HbAc1, and creatinine. Methods. Electronic databases including PUBMED, MEDLINE, and EMBASE were searched for eligible publications to July 2018. The following comparisons between treatment groups were included: normal group versus DN group; control group versus micro/macroalbuminuria group. Results. Twelve eligible studies that included 2500 participants were finally recruited in this meta-analysis. Fifteen miRNAs (miRNA-21, miRNA-181b, miRNA-194, miRNA-30, miRNA-215, and others) were upregulated whereas seven miRNAs (miRNA-26a, miRNA-126, miRNA-424, miRNA-574-3p, miR-223, miR-155, and miR-192) were downregulated in the DN group compared with control groups. The miR-133b, miR-342, miR-30, miR-192, miR-194, and miR-215 were significantly correlated in urinary albumin excretion rates (r=0.33, 95% CI= 0.26-0.39). miR-192, miR-217, miR-15b, miR-34a, and miR-636 were correlated with urinary albumin creatinine rates (r=0.69; 95% CI=0.12-0.92), while miR-133b, miR-345, miR-33, miR-326, miR-574-3p, miR-126, miR-217, miR-15b, miR-34a, and miR-636 were significantly correlated with HbAc1 (r =0.23, 95% CI = 0.15-0.31). There were twelve miRNAs that were closely related to the glomerular filtration rate (r=0.28, 95% CI =0.21-0.34). Creatinine (r=0.33, 95% CI = 0.22-0.40) was significantly different between normal and DN groups. Conclusions. The meta-analysis acquired the correlations between miRNAs and outcomes including UAER, UACR, eGFR, HbAc1, and creatinine in DN. It suggested that miRNAs may participate in the pathogenesis of DN process.

Interactions Among Non-Coding RNAs in Diabetic Nephropathy

“…Whereas, seven miRNAs were downregulated in DN, including miRNA-26a, miRNA-126, miRNA-574-3p, miR-155, and miR-192 (Wang et al, 2019b). Importantly, the UAE rates correlated with these six miRNAs expressions (miR-133b, miR-342, miR-30, miR-192, miR-194, and miR-215), urinary albumin-creatinine ratio associated with five miRNAs expressions (miR-192, miR-217, miR-15b, miR-34a, and miR-636), and the GFR correlated with twelve miRNAs expressions (Eissa et al, 2016b;Wang et al, 2019b).…”

“…MicroRNAs (miRNAs) are the most studied ncRNAs in renalassociated complications (Simpson et al, 2016) (Table 1). Recent systematic review and meta-analysis in 12 of previous DN human studies (Wang et al, 2019b), showed that 15 miRNAs were upregulated in DN, including miRNA-21, miRNA-181b, and miRNA-215. Whereas, seven miRNAs were downregulated in DN, including miRNA-26a, miRNA-126, miRNA-574-3p, miR-155, and miR-192 (Wang et al, 2019b).…”

“…Another oxidative stress-related miRNA is the miR-377, and its expression was higher in the renal tissue of DN mice (Wang et al, 2008), thus caused a reduction in the expression of superoxide dismutase 2 (SOD2), an enzyme responsible for removing free superoxide radicals. Several other miRNAs also regulate endoplasmic reticulum (ER) and oxidative stress in renal cells, such as miR-379 cluster, miR-494 (Kato et al, 2016), miR-15b (Eissa et al, 2016a;Fu et al, 2019;Wang et al, 2019b), and miR-135a (He et al, 2014). Interestingly, miR-214 expression was reduced in peripheral blood of DN mice and overexpression of miR-214 in human renal proximal tubular epithelial cells prevented oxidative stress via upregulation of mitochondrial uncoupling protein-2 (UCP2) expression and its downstream pathway, the ROS/AKT/mTOR signaling pathway with significant reduction of ROS (Yang et al, 2019).…”

lncRNA ZEB1-AS1 inhibits high glucose-induced EMT and fibrogenesis by regulating the miR-216a-5p/BMP7 axis in diabetic nephropathy

“…lncRNAs act as competitive endogenous RNAs (ceRNAs) that competitively bind to miRNAs (18). Recent studies indicated that miRNAs are involved in DN pathogenesis, including microRNA-216a (miR-216a) (19,20). However, the relationship between ZEB1-AS1 and miR-216a-5p in DN development is unknown.…”

The Coming Age of Flavonoids in the Treatment of Diabetic Complications

“…Diabetic nephropathy (DN), one of the most prevalent complications in diabetes, is characterized by a progressive development of renal dysfunction. In the early stage, the first symptom is microalbuminuria (appearance of low levels of albumin in the urine, 30-300 mg/g), which precedes macroalbuminuria (high levels of albumin in the urine, >300 mg/g), leading to a deterioration of renal function and progression to End Stage Renal Disease (ESRD) [64]. Accumulating evidence has clearly demonstrated that immune-inflammatory response plays a paramount role in the onset and progression of diabetic kidney disease.…”