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Current Molecular Medicine


ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

Simultaneous Assessment of MicroRNAs 126 and 192 in Diabetic Nephropathy Patients and the Relation of these MicroRNAs with Urinary Albumin

Author(s): Safaa I. Tayel*, Amany A. Saleh, Sally M. El-Hefnawy, Khaled MA. Elzorkany, Ghada E. Elgarawany and Rasha I. Noreldin

Volume 20 , Issue 5 , 2020

Page: [361 - 371] Pages: 11

DOI: 10.2174/1566524019666191019103918

Price: $65


Background and Objective: Diabetic nephropathy (DN) is a major determinant of end-stage renal disease (ESRD). Altered microRNA levels lead to serious chronic diseases, such as diabetes. We aimed to measure the expression levels of two microRNAs, microRNA126 and 192 in DN and investigate their connection with albuminuria levels.

Methods: This study included 229 subjects (134 DN patients and 95 controls). Serum lipid profiles, glucose levels, glycated haemoglobin (HbA1c) levels, and renal functions were assayed. The microRNA126 and microRNA192 expression levels were determined by real-time PCR.

Results: Patients with DN had higher weights, BMI values, glucose levels (P<0.001), HbA1c levels (P<0.001), urinary albumin-creatinine ratio (ACR) values (P<0.001), urea levels (P=0.002), and creatinine levels (P=0.004) and lower expression levels of both microRNA192 (P<0.001) and microRNA126 (P<0.001) than controls. MicroRNA126 expression was positively correlated with age, estimated glomerular filtration rate (eGFR) and microRNA192 expression but negatively correlated with blood sugar, HbA1c, urea, creatinine and ACR. MicroRNA192 had higher sensitivity (91%), specificity (94%), and area under the curve (AUC) (0.967) values than microRNA126 (sensitivity, 90%; specificity, 68%; AUC, 0.897) and thus can precisely diagnose DN.

Conclusion: Both MicroRNA126 and microRNA192 expression were obviously associated with DN and might determine the progression of the disease owing to prominent relation with macroalbuminuria.

Keywords: Diabetic nephropathy, microalbuminuria, MicroRNA, renal functions, urinary albumin, nephropathy.

Saeedi Borujeni MJ, Esfandiary E, Taheripak G, Codoñer-Franch P, Alonso-Iglesias E, Mirzaei H. Molecular aspects of diabetes mellitus: Resistin, microRNA, and exosome. J Cell Biochem 2018; 119(2): 1257-72.
[] [PMID: 28688216]
Zhang Y, Sun X, Icli B, Feinberg MW. Emerging Roles for MicroRNAs in Diabetic Microvascular Disease: Novel Targets for Therapy. Endocr Rev 2017; 38(2): 145-68.
[] [PMID: 28323921]
Mohan A, Singh RS, Kumari M, et al. Urinary Exosomal microRNA-451-5p Is a Potential Early Biomarker of Diabetic Nephropathy in Rats. PLoS One 2016; 11(4) e0154055
[] [PMID: 27101382]
Delić D, Eisele C, Schmid R, et al. Urinary exosomal miRNA signature in type II diabetic nephropathy patients. PLoS One 2016; 11(3) e0150154
[] [PMID: 26930277]
Barutta F, Bellini S, Mastrocola R, Bruno G, Gruden G. MicroRNA and microvascular complications of diabetes. Int J Endocrinol 2018; 2018 6890501
[] [PMID: 29707000]
Gonzalez Suarez ML, Thomas DB, Barisoni L, Fornoni A. Diabetic nephropathy: Is it time yet for routine kidney biopsy? World J Diabetes 2013; 4(6): 245-55.
[] [PMID: 24379914]
Borchert GM, Lanier W, Davidson BL. RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol 2006; 13(12): 1097-101.
[] [PMID: 17099701]
Ardekani AM, Naeini MM. The role of MicroRNAs in human diseases. Avicenna J Med Biotechnol 2010; 2(4): 161-79.
[PMID: 23407304]
Pandey AK, Agarwal P, Kaur K, Datta M. MicroRNAs in diabetes: tiny players in big disease. Cell Physiol Biochem 2009; 23(4-6): 221-32.
[] [PMID: 19471090]
Bhatt K, Mi Q-S, Dong Z. microRNAs in kidneys: biogenesis, regulation, and pathophysiological roles. Am J Physiol Renal Physiol 2011; 300(3): F602-10.
[] [PMID: 21228106]
Kato M, Arce L, Natarajan R. MicroRNAs and their role in progressive kidney diseases. Clin J Am Soc Nephrol 2009; 4(7): 1255-66.
[] [PMID: 19581401]
Ma X, Lu C, Lv C, Wu C, Wang Q. The expression of miR-192 and its significance in diabetic nephropathy patients with different urine albumin creatinine ratio. J Diabetes Res 2016; 2016 6789402
[] [PMID: 26881255]
Krupa A, Jenkins R, Luo DD, Lewis A, Phillips A, Fraser D. Loss of MicroRNA-192 promotes fibrogenesis in diabetic nephropathy. J Am Soc Nephrol 2010; 21(3): 438-47.
[] [PMID: 20056746]
Fang S, Ma X, Guo S, Lu J. MicroRNA-126 inhibits cell viability and invasion in a diabetic retinopathy model via targeting IRS-1. Oncol Lett 2017; 14(4): 4311-8.
[] [PMID: 28943945]
Harvey SJ, Jarad G, Cunningham J, et al. Podocyte-specific deletion of dicer alters cytoskeletal dynamics and causes glomerular disease. J Am Soc Nephrol 2008; 19(11): 2150-8.
[] [PMID: 18776121]
Zampetaki A, Kiechl S, Drozdov I, et al. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res 2010; 107(6): 810-7.
[] [PMID: 20651284]
Bijkerk R, Duijs JMGJ, Khairoun M, et al. Circulating microRNAs associate with diabetic nephropathy and systemic microvascular damage and normalize after simultaneous pancreas-kidney transplantation. Am J Transplant 2015; 15(4): 1081-90.
[] [PMID: 25716422]
Wang H, Peng W, Shen X, Huang Y, Ouyang X, Dai Y. Circulating levels of inflammation-associated miR-155 and endothelial-enriched miR-126 in patients with end-stage renal disease. Braz J Med Biol Res 2012; 45(12): 1308-14.
[] [PMID: 23070235]
Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998; 15(7): 539-53.
[<539:AID-DIA668>3.0.CO;2-S] [PMID: 9686693]
Mueller P. MaryMacNell S, Jay S and Dayton T. Whitfield laboratory C, The analytical determination of the protein albumin in urine. Clin Chem 1991; 37(2): 191-5.
[PMID: 1993322]
National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002; 39(2)(Suppl. 1): S1-S266.
[PMID: 11904577]
Levey AS, Coresh J, Greene T, et al. Chronic Kidney Disease Epidemiology Collaboration. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 2006; 145(4): 247-54.
[] [PMID: 16908915]
Tuttle KR, Bakris GL, Bilous RW, et al. Diabetic kidney disease: a report from an ADA Consensus Conference. Am J Kidney Dis 2014; 64(4): 510-33.
[] [PMID: 25257325]
Hostetter TH. Prevention of the development and progression of renal disease. J Am Soc Nephrol 2003; 14(7 (Suppl. 2): S144-7.
[] [PMID: 12819320]
Lv C, Zhou YH, Wu C, Shao Y, Lu CL, Wang QY. The changes in miR-130b levels in human serum and the correlation with the severity of diabetic nephropathy. Diabetes Metab Res Rev 2015; 31(7): 717-24.
[] [PMID: 25952368]
Al-Kafaji G, Al-Mahroos G, Al-Muhtaresh HA, Skrypnyk C, Sabry MA, Ramadan AR. Decreased expression of circulating microRNA-126 in patients with type 2 diabetic nephropathy: A potential blood-based biomarker. Exp Ther Med 2016; 12(2): 815-22.
[] [PMID: 27446281]
Chien H-Y, Chen C-Y, Chiu Y-H, Lin Y-C, Li W-C. Differential microRNA profiles predict diabetic nephropathy progression in Taiwan. Int J Med Sci 2016; 13(6): 457-65.
[] [PMID: 27279796]
Shao Y, Ren H, Lv C, Ma X, Wu C, Wang Q. Changes of serum Mir-217 and the correlation with the severity in type 2 diabetes patients with different stages of diabetic kidney disease. Endocrine 2017; 55(1): 130-8.
[] [PMID: 27522360]
Szeto C-C, Ching-Ha KB, Ka-Bik L, et al. Micro-RNA expression in the urinary sediment of patients with chronic kidney diseases. Dis Markers 2012; 33(3): 137-44.
[] [PMID: 22960330]
Wang G, Kwan BC-H, Lai FM-M, Chow K-M, Li PK-T, Szeto C-C. Urinary sediment miRNA levels in adult nephrotic syndrome. Clin Chim Acta 2013; 418: 5-11.
[] [PMID: 23313053]
Park S, Moon S, Lee K, Park IB, Lee DH, Nam S. Urinary and blood MicroRNA-126 and -770 are potential noninvasive biomarker candidates for diabetic nephropathy: a meta-analysis. Cell Physiol Biochem 2018; 46(4): 1331-40.
[] [PMID: 29689545]
Jaeger A, Zollinger L, Saely CH, et al. Circulating microRNAs -192 and -194 are associated with the presence and incidence of diabetes mellitus. Sci Rep 2018; 8(1): 14274.
[] [PMID: 30250222]
Ezzat H, Lotfy AM, Attia FA, Mohamed GA, Tawfeek HM. Expression of micro RNA192 in type 2 diabetes mellitus relation to glycemic control, metabolic abnormalities, renal and ocular complications. Am J Biochem 2013; 3(4): 97-106.
Rezk NA, Sabbah NA, Saad MSS. Role of MicroRNA 126 in screening, diagnosis, and prognosis of diabetic patients in Egypt. IUBMB Life 2016; 68(6): 452-8.
[] [PMID: 27118517]
Pencina MJ, D’Agostino RB Sr, D’Agostino RB Jr, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 2008; 27(2): 157-72.
[] [PMID: 17569110]
Gil-Zamorano J, Martin R, Daimiel L, et al. Docosahexaenoic acid modulates the enterocyte Caco-2 cell expression of microRNAs involved in lipid metabolism. J Nutr 2014; 144(5): 575-85.
[] [PMID: 24623846]
Hernández-Alonso P, Giardina S, Salas-Salvadó J, Arcelin P, Bulló M. Chronic pistachio intake modulates circulating microRNAs related to glucose metabolism and insulin resistance in prediabetic subjects. Eur J Nutr 2017; 56(6): 2181-91.
[] [PMID: 27383196]
Jiang L, Huang J, Chen Y, et al. Identification of several circulating microRNAs from a genome-wide circulating microRNA expression profile as potential biomarkers for impaired glucose metabolism in polycystic ovarian syndrome. Endocrine 2016; 53(1): 280-90.
[] [PMID: 26860517]
Wang S, Aurora AB, Johnson BA, et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell 2008; 15(2): 261-71.
[] [PMID: 18694565]
Kato M, Arce L, Wang M, Putta S, Lanting L, Natarajan R. A microRNA circuit mediates transforming growth factor-β1 autoregulation in renal glomerular mesangial cells. Kidney Int 2011; 80(4): 358-68.
[] [PMID: 21389977]
Feng X, Wang H, Ye S, et al. Up-regulation of microRNA-126 may contribute to pathogenesis of ulcerative colitis via regulating NF-kappaB inhibitor IκBα. PLoS One 2012; 7(12) e52782
[] [PMID: 23285182]
Li Z, Lu J, Sun M, et al. Distinct microRNA expression profiles in acute myeloid leukemia with common translocations. Proc Natl Acad Sci USA 2008; 105(40): 15535-40.
Feng R, Chen X, Yu Y, et al. miR-126 functions as a tumour suppressor in human gastric cancer. Cancer Lett 2010; 298(1): 50-63.
Crawford M, Brawner E, Batte K, et al. Nana-Sinkam SP MicroRNA-126 inhibits invasion in non-small cell lung carcinoma cell lines. Biochem Biophys Res Commun 2008; 373(4): 607-12.
Tan Y, Ge G, Pan T, et al. A serum microRNA panel as potential biomarkers for hepatocellular carcinoma related with hepatitis B virus. PLoS One 2014; 9(9) e107986
[] [PMID: 25238238]
Feinberg-Gorenshtein G, Guedj A, Shichrur K, et al. MiR-192 directly binds and regulates Dicer1 expression in neuroblastoma. PLoS One 2013; 8(11) e78713
[] [PMID: 24223844]
Jin Z, Selaru FM, Cheng Y, et al. MicroRNA-192 and -215 are upregulated in human gastric cancer in vivo and suppress ALCAM expression in vitro. Oncogene 2011; 30(13): 1577-85.
[] [PMID: 21119604]
Song B, Wang Y, Kudo K, Gavin EJ, Xi Y, Ju J. miR-192 Regulates dihydrofolate reductase and cellular proliferation through the p53-microRNA circuit. Clin Cancer Res 2008; 14(24): 8080-6.
[] [PMID: 19088023]
Schotte D, De Menezes RX, Akbari Moqadam F, et al. MicroRNA characterize genetic diversity and drug resistance in pediatric acute lymphoblastic leukemia. Haematologica 2011; 96(5): 703-11.
[] [PMID: 21242186]

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