MicroRNA-21 As an Early Marker of Nephropathy in Patients with Type 1 Diabetes

Overview

Journal Indian J Nephrol

Specialty Nephrology

Date 2020 Feb 5

PMID 32015595

Citations 13

Authors

Mohamed Fouad

Ibrahim Salem

Khaled Elhefnawy

Nermin Raafat

Amal Faisal

Affiliations

Soon will be listed here.

Abstract

Introduction: Diabetic nephropathy (DN) is the most common cause of chronic kidney disease worldwide. A major challenge is to identify early diabetic nephropathy. microRNAs (miRNAs) are short noncoding RNA sequences and regulate a wide range of biological processes as cell differentiation, proliferation, cell metabolism and apoptosis. miRNAs may have a role in molecular mechanisms linked to cellular pathways of DN. The aim of this study was to investigate the level of microRNA-21 as a potential marker of early nephropathy in type 1 diabetes mellitus (T1DM).

Methods: A total number of 340 participants were included and classified into 3 groups; Group I included 100 healthy participants, Group II included 120 patients with T1DM with <5 years duration, and Group III included 120 patients with T1DM with >5 years duration. All participants were submitted to detail clinical examination, laboratory investigations, urinary albumin/creatinine ratio (ACR), estimated glomerular filtration rate (eGFR) as well as plasma microRNA-21 assays.

Results: Blood pressure and ACR were significantly higher in group III than groups I and II. Further, microRNA-21 was significantly higher in group III than groups I and II, and more in group II than group I. microRNA-21 starts to rise in group II before microalbuminuria. miRNA-21 at a level of 0.01 had a greater sensitivity 94.1% and specificity 100% for identifying DN than ACR at level 45 mg/gm with sensitivity 88.2% and specificity 89%.

Conclusion: Plasma microRNA-21 can serve as an early marker for diagnosis and identifying diabetic nephropathy in T1DM.

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References

Dugbartey G . Diabetic nephropathy: A potential savior with 'rotten-egg' smell. Pharmacol Rep. 2017; 69(2):331-339. DOI: 10.1016/j.pharep.2016.11.004. View

Jensen T, Borch-Johnsen K, Deckert T . Changes in blood pressure and renal function in patients with type I (insulin-dependent) diabetes mellitus prior to clinical diabetic nephropathy. Diabetes Res. 1987; 4(4):159-62. View

. Diabetic nephropathy. Diabetes Care. 2002; 23 Suppl 1:S69-72. View

Creemers E, Tijsen A, Pinto Y . Circulating microRNAs: novel biomarkers and extracellular communicators in cardiovascular disease?. Circ Res. 2012; 110(3):483-95. DOI: 10.1161/CIRCRESAHA.111.247452. View

Levey A, Stevens L, Schmid C, Zhang Y, Castro 3rd A, Feldman H . A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009; 150(9):604-12. PMC: 2763564. DOI: 10.7326/0003-4819-150-9-200905050-00006. View

Giunti S, Barit D, Cooper M . Mechanisms of diabetic nephropathy: role of hypertension. Hypertension. 2006; 48(4):519-26. DOI: 10.1161/01.HYP.0000240331.32352.0c. View

Chau B, Xin C, Hartner J, Ren S, Castano A, Linn G . MicroRNA-21 promotes fibrosis of the kidney by silencing metabolic pathways. Sci Transl Med. 2012; 4(121):121ra18. PMC: 3672221. DOI: 10.1126/scitranslmed.3003205. View

Koya D, Jirousek M, Lin Y, Ishii H, Kuboki K, King G . Characterization of protein kinase C beta isoform activation on the gene expression of transforming growth factor-beta, extracellular matrix components, and prostanoids in the glomeruli of diabetic rats. J Clin Invest. 1997; 100(1):115-26. PMC: 508171. DOI: 10.1172/JCI119503. View

Naidoo D . The link between microalbuminuria, endothelial dysfunction and cardiovascular disease in diabetes. Cardiovasc J S Afr. 2002; 13(4):194-9. View

10.

Ishii H, Jirousek M, Koya D, Takagi C, Xia P, Clermont A . Amelioration of vascular dysfunctions in diabetic rats by an oral PKC beta inhibitor. Science. 1996; 272(5262):728-31. DOI: 10.1126/science.272.5262.728. View

11.

Miranda K, Huynh T, Tay Y, Ang Y, Tam W, Thomson A . A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes. Cell. 2006; 126(6):1203-17. DOI: 10.1016/j.cell.2006.07.031. View

12.

Tabaei B, Al-Kassab A, Ilag L, Zawacki C, Herman W . Does microalbuminuria predict diabetic nephropathy?. Diabetes Care. 2001; 24(9):1560-6. DOI: 10.2337/diacare.24.9.1560. View

13.

Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M . MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008; 456(7224):980-4. DOI: 10.1038/nature07511. View

14.

Greco S, Fasanaro P, Castelvecchio S, DAlessandra Y, Arcelli D, Di Donato M . MicroRNA dysregulation in diabetic ischemic heart failure patients. Diabetes. 2012; 61(6):1633-41. PMC: 3357263. DOI: 10.2337/db11-0952. View

15.

Koya D, King G . Protein kinase C activation and the development of diabetic complications. Diabetes. 1998; 47(6):859-66. DOI: 10.2337/diabetes.47.6.859. View

16.

Osipova J, Fischer D, Dangwal S, Volkmann I, Widera C, Schwarz K . Diabetes-associated microRNAs in pediatric patients with type 1 diabetes mellitus: a cross-sectional cohort study. J Clin Endocrinol Metab. 2014; 99(9):E1661-5. DOI: 10.1210/jc.2013-3868. View

17.

Hovind P, Tarnow L, Rossing P, Jensen B, Graae M, Torp I . Predictors for the development of microalbuminuria and macroalbuminuria in patients with type 1 diabetes: inception cohort study. BMJ. 2004; 328(7448):1105. PMC: 406322. DOI: 10.1136/bmj.38070.450891.FE. View

18.

Vickers K, Palmisano B, Shoucri B, Shamburek R, Remaley A . MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol. 2011; 13(4):423-33. PMC: 3074610. DOI: 10.1038/ncb2210. View

19.

Rother K . Diabetes treatment--bridging the divide. N Engl J Med. 2007; 356(15):1499-501. PMC: 4152979. DOI: 10.1056/NEJMp078030. View

20.

Assmann T, Recamonde-Mendoza M, de Souza B, Crispim D . MicroRNA expression profiles and type 1 diabetes mellitus: systematic review and bioinformatic analysis. Endocr Connect. 2017; 6(8):773-790. PMC: 5682418. DOI: 10.1530/EC-17-0248. View