Differential microRNA Profiles Predict Diabetic Nephropathy Progression in Taiwan

Abstract

Objectives: Diabetic nephropathy (DN) is a major leading cause of kidney failure. Recent studies showed that serological microRNAs (miRs) could be utilized as biomarkers to identify disease pathogenesis; the DN-related miRs, however, remained to be explored. Methods: A prospective case-control study was conducted. The clinical significance of five potential miRs (miR-21, miR-29a, miR-29b, miR-29c and miR192) in type 2 Diabetes Mellitus (T2DM) patients who have existing diabetic retinopathy with differential Albumin:Creatinine Ratio (ACR) and estimated Glomerular Filtration Rate (eGFR) was performed using quantitative RT-PCR analysis. The subjects with diabetic retinopathy enrolled in Taipei City Hospital, Taiwan, were classified into groups of normal albuminuria (ACR<30mg/g; N=12); microalbuminuria (30mg/g<ACR<300mg/g; N=17) and overt proteinuria (ACR>300mg/g; N=21) as well as 18 low-eGFR (eGFR<60ml/min) and 32 high-eGFR (eGFR>60ml/min). The level of serum miRs was statistically correlated with age, Glucose AC, ACR, eGFR and DN progression. Results: The levels of miR-21, miR-29a and miR-192 were significantly enriched in the overt proteinuria group compared with microalbuminuria and/or overt proteinuria groups. It was shown that only miR-21 level was significantly up-regulated in low-eGFR group compared with high-eGFR patients. Interestingly, Pearson's correlation coefficient analysis demonstrated that DN progressors showed significantly greater levels of miR-21, miR-29a, miR-29b and miR-29c in comparison with non-progressors implying the clinical potential of DN associated miRs in monitoring and preventing disease advancement. Conclusion: Our findings showed that miR-21, miR-29a/b/c and miR-192 could reflect DN pathogenesis and serve as biomarkers during DN progression.

Regulatory Roles of MicroRNAs in Diabetes

“…For instance, diabetic nephropathy (DN) is one of the most serious complications of diabetes. Recently, a prospective case-control study showed that miR-21 , miR-29a/b/c , and miR-192 reflect DN pathogenesis and could be of clinical significance to monitor and prevent DN advancement [66]. miR-21 was shown to suppress PTEN , a key modulator in DN [67]; miR-192 was shown to suppress ZEB2 , which is responsible for controlling TGF-β-induced extracellular matrix proteins accumulating during DN [67], while miR-29c was shown to inhibit SPRY1 , which involves albuminuria and kidney mesangial matrix accumulation in diabetic mice models [68].…”

Identification of genes and signaling pathways associated with diabetic neuropathy using a weighted correlation network analysis

“…There is in vivo evidence that microRNA (miR)-29c knockdown or miR-27a knockdown compromises progression of diabetic nephropathy. [8,9] Furthermore, Chien et al [10] have found that miR-21, miR-29a/b/c, and miR-192 are involved in pathogenesis of diabetic neuropathy and might be suggested as biomarkers of progression of diabetic neuropathy. Despite these achievements, the molecular mechanisms behind the diabetic neuropathy have not been fully elucidated.…”

MicroRNA‐326‐3p ameliorates high glucose and ox‐LDL‐IC‐ induced fibrotic injury in renal mesangial cells by targeting FcγRIII

“…Mountainous research has demonstrated that altered levels of miRNAs were involved in the progression of many diseases, DKD included. Increasing studies have proved that in the progression of DKD, various miRNAs had positive correlation with fibrosis such as miR‐21, miR‐192, miR‐377 and miR‐491, while miR‐23b, miR‐29a, miR‐29b and miR‐200 were the opposite . Our previous bioinformatical study has found the expression of miR‐326‐3p in kidney tissue was significantly decreased in patients with DKD compared with the normal control .…”

“…Increasing studies have proved that in the progression of DKD, various miRNAs had positive correlation with fibrosis such as miR-21, miR-192, miR-377 and miR-491, while miR-23b, miR-29a, miR-29b and miR-200 were the opposite. 28,29 Our previous bioinformatical study has found the expression of miR-326-3p in kidney tissue was significantly decreased in patients with DKD compared with the normal control. 20 Recently, miR-326-3p was identified to be an important regulator of fibrosis in idiopathic pulmonary fibrosis (ITP), lung cancer and systemic lupus erythematosus (SLE).…”