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Int J Med Sci 2016; 13(6):457-465. doi:10.7150/ijms.15548 This issue Cite

Research Paper

Differential microRNA Profiles Predict Diabetic Nephropathy Progression in Taiwan

Hung-Yu Chien^1*, Chang-Yi Chen^2*, Yen-Hui Chiu³, Yi-Chun Lin^4,5, Wan-Chun Li^2,3✉

1. Department of Endocrinology & Metabolism, Taipei City Hospital, Ren-Ai Branch, Taipei, Taiwan;
2. Institute of Oral Biology and Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan;
3. Department of Education and Research, Taipei City Hospital, Taipei, Taiwan;
4. Division of Endocrinology &Metabolism, Taipei Veterans General Hospital, Taipei, Taiwan;
5. Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan;
*These authors contributed equally.

✉ Corresponding author: Wan-Chun Li, Ph.D. Institute of Oral Biology and Department of Dentistry, School of Dentistry, National Yang-Ming University, No.155, Sec.2, Li-Nong St, Taipei, 11221, Taiwan. Phone: +886-2-28267255; Fax: +886-2-28264053; E-mail: wcliedu.tw. More

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.

Keywords: Albumin:creatinine ratio, Biomarkers, Circulating microRNA, Diabetic nephropathy, Estimated Glomerular Filtration Rate.

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