diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM8237diaendo-8237Research ArticleВопросы патогенезаPathogenesisСовременные представления о роли микроРНК при диабетической нефропатии: потенциальные биомаркеры и мишени таргетной терапииNew insights on microRNAs in diabetic nephropathy: potential biomarkers for diagnosis and therapeutic targetshttps://orcid.org/0000-0002-1823-0125КамышоваЕлена СергеевнаKamyshovaElena Sergeevna

кандидат медицинский наук, старший научный сотрудник НИО нефрологии НИЦ

MD, PhD, senior research associate

kamyshova-es@yandex.ruhttps://orcid.org/0000-0002-8007-5680БобковаИрина НиколаевнаBobkovaIrina Nikolaevna

Доктор медицинский наук, старший научный сотрудник НИО нефрологии НИЦ

MD, PhD

irbo.mma@mail.ruhttps://orcid.org/0000-0001-8529-3081КутыринаИрина МихайловнаKutyrinaIrina Mikhailovna

доктор медицинских наук, профессор кафедры нефрологии и гемодиализа ИПО

MD, PhD, Professor

kutyrina-im@yandex.ru<p>ФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет)</p>Россия<p>I.M.Sechenov First Moscow State Medical University</p>Russian Federation2017110520172014250Copyright &#x00A9; Камышова Е.С., Бобкова И.Н., Кутырина И.М., 20172017Камышова Е.С., Бобкова И.Н., Кутырина И.М.Kamyshova E.S., Bobkova I.N., Kutyrina I.M.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/8237

Диабетическая нефропатия (ДН) – тяжелое осложнение сахарного диабета, ассоциированное с прогрессирующим снижением функции почек. Микроальбуминурия представляет собой «золотой стандарт» диагностики ДН, однако прогностическая значимость и специфичность этого метода в выявлении диабетического поражения почек ограничены, в связи с чем ведется активный поиск новых биомаркеров для диагностики ДН, в том числе ранней. В моделях ДН in vitro и in vivo продемонстрирована важная роль микроРНК (коротких некодирующих РНК, которые, ингибируя экспрессию генов-мишеней, модулируют физиологические и патологические процессы) в развитии ДН. Недавние исследования показали, что нарушение регуляции микроРНК, ассоциированное с такими характерными признаками ДН, как расширение мезангия и накопление белков экстрацеллюлярного матрикса, тесно связано с фиброзом и гломерулосклерозом. Это дало основание рассматривать увеличение или снижение экспрессии отдельных микроРНК в почечной ткани или биологических жидкостях (в том числе в моче) в качестве новых биомаркеров для диагностики и мониторирования ДН, перспективных направлений таргетной терапии. В настоящем обзоре представлены результаты последних экспериментальных и клинических исследований по данным вопросам.

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus associated with the progressive deterioration of renal function. Although microalbuminuria is considered as a gold standard for DN diagnosis, it has limited predictive powers and specificity as a diagnostic tool for the early stage of DN. Therefore, new biomarkers are required for the early detection of DN. Studies using in vitro and in vivo models of DN have revealed an important role of microRNAs (miRNAs), short non-coding RNAs that modulate physiological and pathological processes by inhibiting target gene expression, in DN development. Recent studies have shown that the dysregulation of miRNAs, which is associated with the key features of DN, such as the mesangial expansion and accumulation of extracellular matrix proteins, is related to fibrosis and glomerular dysfunction. Thus, the up- and downregulation of miRNA expression in the renal tissue or biological fluids, including urine, may represent new biomarkers for the diagnosis and monitoring of DN progression. In this review, we highlight the significance of miRNAs as biomarkers for the early detection of DN and emphasise their potential role as a therapeutic target.

диабетическая нефропатиябиомаркермикроРНКdiabetic nephropathybiomarkermiRNAReferencesШестакова М.В., Шамхалова М.Ш., Ярек-Мартынова И.Я., и др. Сахарный диабет и хроническая болезнь почек: достижения, нерешенные проблемы и перспективы лечения // Сахарный диабет. – 2011. – Т. 14. – №1. – C. 81-88. [Shestakova MV, Shamkhalova MS, Yarek-Martynova IY, Klefortova II, Sukhareva OY, Vikulova OK, et al. Diabetes mellitus and chronic kidney disease: achievements, unresolved problems, and prospects for therapy. Diabetes mellitus. 2011;14(1):81-88. (In Russ).] doi: 10.14341/2072-0351-6254Шестакова М.В., Шамхалова М.Ш., Ярек-Мартынова И.Я., и др. Сахарный диабет и хроническая болезнь почек: достижения, нерешенные проблемы и перспективы лечения // Сахарный диабет. – 2011. – Т. 14. – №1. – C. 81-88. [Shestakova MV, Shamkhalova MS, Yarek-Martynova IY, Klefortova II, Sukhareva OY, Vikulova OK, et al. Diabetes mellitus and chronic kidney disease: achievements, unresolved problems, and prospects for therapy. Diabetes mellitus. 2011;14(1):81-88. (In Russ).] doi: 10.14341/2072-0351-6254Caramori ML, Fioretto P, Mauer M. The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient? Diabetes. 2000;49(9):1399-1408. doi: 10.2337/diabetes.49.9.1399Caramori ML, Fioretto P, Mauer M. The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient? Diabetes. 2000;49(9):1399-1408. doi: 10.2337/diabetes.49.9.1399Okamura K, Hagen JW, Duan H, et al. The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila. Cell. 2007;130(1):89-100. doi: 10.1016/j.cell.2007.06.028Okamura K, Hagen JW, Duan H, et al. The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila. Cell. 2007;130(1):89-100. doi: 10.1016/j.cell.2007.06.028Баулина Н.М., Кулакова О.Г., Фаворова О.О. МикроРНК: роль в развитии аутоиммунного воспаления. // ActaNature (русскоязычная версия). – 2016. – Т. 8. – №1. – С. 21-33. [Baulina NM, Kulakova OG, Favorova OO. MicroRNAs: The Role in Autoimmune Inflammation. Acta Nature. 2016;8(1):21-33 (In Russ)]Баулина Н.М., Кулакова О.Г., Фаворова О.О. МикроРНК: роль в развитии аутоиммунного воспаления. // ActaNature (русскоязычная версия). – 2016. – Т. 8. – №1. – С. 21-33. [Baulina NM, Kulakova OG, Favorova OO. MicroRNAs: The Role in Autoimmune Inflammation. Acta Nature. 2016;8(1):21-33 (In Russ)]Zhuo Y, Gao G, Shi JA, et al. miRNAs: biogenesis, origin and evolution, functions on virus-host interaction. Cell Physiol Biochem. 2013;32(3):499-510. doi: 10.1159/000354455Zhuo Y, Gao G, Shi JA, et al. miRNAs: biogenesis, origin and evolution, functions on virus-host interaction. Cell Physiol Biochem. 2013;32(3):499-510. doi: 10.1159/000354455Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 2014;15(8):509-524. doi: 10.1038/nrm3838Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 2014;15(8):509-524. doi: 10.1038/nrm3838Dalmay T. Mechanism of miRNA-mediated repression of mRNA translation. Essays Biochem. 2013;54:29-38. doi: 10.1042/bse0540029Dalmay T. Mechanism of miRNA-mediated repression of mRNA translation. Essays Biochem. 2013;54:29-38. doi: 10.1042/bse0540029Vasudevan S. Posttranscriptional upregulation by microRNAs. Wiley Interdiscip Rev RNA. 2012;3(3):311-330. doi: 10.1002/wrna.121Vasudevan S. Posttranscriptional upregulation by microRNAs. Wiley Interdiscip Rev RNA. 2012;3(3):311-330. doi: 10.1002/wrna.121Friedlander MR, Lizano E, Houben AJ, et al. Evidence for the biogenesis of more than 1,000 novel human microRNAs. Genome Biol. 2014;15(4):R57. doi: 10.1186/gb-2014-15-4-r57Friedlander MR, Lizano E, Houben AJ, et al. Evidence for the biogenesis of more than 1,000 novel human microRNAs. Genome Biol. 2014;15(4):R57. doi: 10.1186/gb-2014-15-4-r57Weber JA, Baxter DH, Zhang S, et al. The microRNA spectrum in 12 body fluids. Clin Chem. 2010;56(11):1733-1741. doi: 10.1373/clinchem.2010.147405Weber JA, Baxter DH, Zhang S, et al. The microRNA spectrum in 12 body fluids. Clin Chem. 2010;56(11):1733-1741. doi: 10.1373/clinchem.2010.147405Weickmann JL, Glitz DG. Human ribonucleases. Quantitation of pancreatic-like enzymes in serum, urine, and organ preparations. Journal Of Biological Chemistry. 1982;257:8705-8710.Weickmann JL, Glitz DG. Human ribonucleases. Quantitation of pancreatic-like enzymes in serum, urine, and organ preparations. Journal Of Biological Chemistry. 1982;257:8705-8710.Beltrami C, Clayton A, Phillips AO, et al. Analysis of urinary microRNAs in chronic kidney disease. Biochem Soc Trans. 2012;40(4):875-879. doi: 10.1042/BST20120090Beltrami C, Clayton A, Phillips AO, et al. Analysis of urinary microRNAs in chronic kidney disease. Biochem Soc Trans. 2012;40(4):875-879. doi: 10.1042/BST20120090Shi S, Yu L, Chiu C, et al. Podocyte-selective deletion of dicer induces proteinuria and glomerulosclerosis. J Am Soc Nephrol. 2008;19(11):2159-2169. doi: 10.1681/ASN.2008030312Shi S, Yu L, Chiu C, et al. Podocyte-selective deletion of dicer induces proteinuria and glomerulosclerosis. J Am Soc Nephrol. 2008;19(11):2159-2169. doi: 10.1681/ASN.2008030312Harvey 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):2150-2158. doi: 10.1681/ASN.2008020233Harvey 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):2150-2158. doi: 10.1681/ASN.2008020233Ho J, Ng KH, Rosen S, et al. Podocyte-specific loss of functional microRNAs leads to rapid glomerular and tubular injury. J Am Soc Nephrol. 2008;19(11):2069-2075. doi: 10.1681/ASN.2008020162Ho J, Ng KH, Rosen S, et al. Podocyte-specific loss of functional microRNAs leads to rapid glomerular and tubular injury. J Am Soc Nephrol. 2008;19(11):2069-2075. doi: 10.1681/ASN.2008020162Patel V, Hajarnis S, Williams D, et al. MicroRNAs regulate renal tubule maturation through modulation of Pkd1. J Am Soc Nephrol. 2012;23(12):1941-1948. doi: 10.1681/ASN.2012030321Patel V, Hajarnis S, Williams D, et al. MicroRNAs regulate renal tubule maturation through modulation of Pkd1. J Am Soc Nephrol. 2012;23(12):1941-1948. doi: 10.1681/ASN.2012030321Sequeira-Lopez ML, Weatherford ET, Borges GR, et al. The microRNA-processing enzyme dicer maintains juxtaglomerular cells. J Am Soc Nephrol. 2010;21(3):460-467. doi: 10.1681/ASN.2009090964Sequeira-Lopez ML, Weatherford ET, Borges GR, et al. The microRNA-processing enzyme dicer maintains juxtaglomerular cells. J Am Soc Nephrol. 2010;21(3):460-467. doi: 10.1681/ASN.2009090964Sun Y, Koo S, White N, et al. Development of a micro-array to detect human and mouse microRNAs and characterization of expression in human organs. Nucleic Acids Res. 2004;32(22):e188. doi: 10.1093/nar/gnh186Sun Y, Koo S, White N, et al. Development of a micro-array to detect human and mouse microRNAs and characterization of expression in human organs. Nucleic Acids Res. 2004;32(22):e188. doi: 10.1093/nar/gnh186Tian Z, Greene AS, Pietrusz JL, et al. MicroRNA-target pairs in the rat kidney identified by microRNA microarray, proteomic, and bioinformatic analysis. Genome Res. 2008;18(3):404-411. doi: 10.1101/gr.6587008Tian Z, Greene AS, Pietrusz JL, et al. MicroRNA-target pairs in the rat kidney identified by microRNA microarray, proteomic, and bioinformatic analysis. Genome Res. 2008;18(3):404-411. doi: 10.1101/gr.6587008Kanwar YS, Sun L, Xie P, et al. A glimpse of various pathogenetic mechanisms of diabetic nephropathy. Annu Rev Pathol. 2011;6:395-423. doi: 10.1146/annurev.pathol.4.110807.092150Kanwar YS, Sun L, Xie P, et al. A glimpse of various pathogenetic mechanisms of diabetic nephropathy. Annu Rev Pathol. 2011;6:395-423. doi: 10.1146/annurev.pathol.4.110807.092150Qian Y, Feldman E, Pennathur S, et al. From fibrosis to sclerosis: mechanisms of glomerulosclerosis in diabetic nephropathy. Diabetes. 2008;57(6):1439-1445. doi: 10.2337/db08-0061Qian Y, Feldman E, Pennathur S, et al. From fibrosis to sclerosis: mechanisms of glomerulosclerosis in diabetic nephropathy. Diabetes. 2008;57(6):1439-1445. doi: 10.2337/db08-0061Schrijvers BF, De Vriese AS, Flyvbjerg A. From hyperglycemia to diabetic kidney disease: the role of metabolic, hemodynamic, intracellular factors and growth factors/cytokines. Endocr Rev. 2004;25(6):971-1010. doi: 10.1210/er.2003-0018Schrijvers BF, De Vriese AS, Flyvbjerg A. From hyperglycemia to diabetic kidney disease: the role of metabolic, hemodynamic, intracellular factors and growth factors/cytokines. Endocr Rev. 2004;25(6):971-1010. doi: 10.1210/er.2003-0018Chen S, Jim B, Ziyadeh FN. Diabetic nephropathy and transforming growth factor-β: transforming our view of glomerulosclerosis and fibrosis build-up. Seminars in Nephrology. 2003;23(6):532-543. doi: 10.1053/s0270-9295(03)00132-3Chen S, Jim B, Ziyadeh FN. Diabetic nephropathy and transforming growth factor-β: transforming our view of glomerulosclerosis and fibrosis build-up. Seminars in Nephrology. 2003;23(6):532-543. doi: 10.1053/s0270-9295(03)00132-3Liu Y. New insights into epithelial-mesenchymal transition in kidney fibrosis. J Am Soc Nephrol. 2010;21(2):212-222. doi: 10.1681/ASN.2008121226Liu Y. New insights into epithelial-mesenchymal transition in kidney fibrosis. J Am Soc Nephrol. 2010;21(2):212-222. doi: 10.1681/ASN.2008121226Li Y, Kang YS, Dai C, et al. Epithelial-to-mesenchymal transition is a potential pathway leading to podocyte dysfunction and proteinuria. Am J Pathol. 2008;172(2):299-308. doi: 10.2353/ajpath.2008.070057Li Y, Kang YS, Dai C, et al. Epithelial-to-mesenchymal transition is a potential pathway leading to podocyte dysfunction and proteinuria. Am J Pathol. 2008;172(2):299-308. doi: 10.2353/ajpath.2008.070057Hayashida T, Poncelet AC, Hubchak SC, Schnaper HW. TGF-beta1 activates MAP kinase in human mesangial cells: a possible role in collagen expression. Kidney Int. 1999;56(5):1710-1720. doi: 10.1046/j.1523-1755.1999.00733.xHayashida T, Poncelet AC, Hubchak SC, Schnaper HW. TGF-beta1 activates MAP kinase in human mesangial cells: a possible role in collagen expression. Kidney Int. 1999;56(5):1710-1720. doi: 10.1046/j.1523-1755.1999.00733.xKato M, Yuan H, Xu ZG, et al. Role of the Akt/FoxO3a pathway in TGF-beta1-mediated mesangial cell dysfunction: a novel mechanism related to diabetic kidney disease. J Am Soc Nephrol. 2006;17(12):3325-3335. doi: 10.1681/ASN.2006070754Kato M, Yuan H, Xu ZG, et al. Role of the Akt/FoxO3a pathway in TGF-beta1-mediated mesangial cell dysfunction: a novel mechanism related to diabetic kidney disease. J Am Soc Nephrol. 2006;17(12):3325-3335. doi: 10.1681/ASN.2006070754Kato M, Natarajan R. MicroRNAs in diabetic nephropathy: functions, biomarkers, and therapeutic targets. Ann N Y Acad Sci. 2015;1353:72-88. doi: 10.1111/nyas.12758Kato M, Natarajan R. MicroRNAs in diabetic nephropathy: functions, biomarkers, and therapeutic targets. Ann N Y Acad Sci. 2015;1353:72-88. doi: 10.1111/nyas.12758Kato M, Zhang J, Wang M, et al. MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors. Proc Natl Acad Sci U S A. 2007;104(9):3432-3437. doi: 10.1073/pnas.0611192104Kato M, Zhang J, Wang M, et al. MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors. Proc Natl Acad Sci U S A. 2007;104(9):3432-3437. doi: 10.1073/pnas.0611192104Kato M, Arce L, Wang M, et al. A microRNA circuit mediates transforming growth factor-beta1 autoregulation in renal glomerular mesangial cells. Kidney Int. 2011;80(4):358-368. doi: 10.1038/ki.2011.43Kato M, Arce L, Wang M, et al. A microRNA circuit mediates transforming growth factor-beta1 autoregulation in renal glomerular mesangial cells. Kidney Int. 2011;80(4):358-368. doi: 10.1038/ki.2011.43Kato M, Putta S, Wang M, et al. TGF-beta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN. Nat Cell Biol. 2009;11(7):881-889. doi: 10.1038/ncb1897Kato M, Putta S, Wang M, et al. TGF-beta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN. Nat Cell Biol. 2009;11(7):881-889. doi: 10.1038/ncb1897Wang Q, Wang Y, Minto AW, et al. MicroRNA-377 is up-regulated and can lead to increased fibronectin production in diabetic nephropathy. FASEB J. 2008;22(12):4126-4135. doi: 10.1096/fj.08-112326Wang Q, Wang Y, Minto AW, et al. MicroRNA-377 is up-regulated and can lead to increased fibronectin production in diabetic nephropathy. FASEB J. 2008;22(12):4126-4135. doi: 10.1096/fj.08-112326He F, Peng F, Xia X, et al. MiR-135a promotes renal fibrosis in diabetic nephropathy by regulating TRPC1. Diabetologia. 2014;57(8):1726-1736. doi: 10.1007/s00125-014-3282-0He F, Peng F, Xia X, et al. MiR-135a promotes renal fibrosis in diabetic nephropathy by regulating TRPC1. Diabetologia. 2014;57(8):1726-1736. doi: 10.1007/s00125-014-3282-0Wang B, Komers R, Carew R, et al. Suppression of microRNA-29 expression by TGF-beta1 promotes collagen expression and renal fibrosis. J Am Soc Nephrol. 2012;23(2):252-265. doi: 10.1681/ASN.2011010055Wang B, Komers R, Carew R, et al. Suppression of microRNA-29 expression by TGF-beta1 promotes collagen expression and renal fibrosis. J Am Soc Nephrol. 2012;23(2):252-265. doi: 10.1681/ASN.2011010055Chen HY, Zhong X, Huang XR, et al. MicroRNA-29b inhibits diabetic nephropathy in db/db mice. Mol Ther. 2014;22(4):842-853. doi: 10.1038/mt.2013.235Chen HY, Zhong X, Huang XR, et al. MicroRNA-29b inhibits diabetic nephropathy in db/db mice. Mol Ther. 2014;22(4):842-853. doi: 10.1038/mt.2013.235Lin CL, Lee PH, Hsu YC, et al. MicroRNA-29a promotion of nephrin acetylation ameliorates hyperglycemia-induced podocyte dysfunction. J Am Soc Nephrol. 2014;25(8):1698-1709. doi: 10.1681/ASN.2013050527Lin CL, Lee PH, Hsu YC, et al. MicroRNA-29a promotion of nephrin acetylation ameliorates hyperglycemia-induced podocyte dysfunction. J Am Soc Nephrol. 2014;25(8):1698-1709. doi: 10.1681/ASN.2013050527Kanasaki K, Shi S, Kanasaki M, et al. Linagliptin-mediated DPP-4 inhibition ameliorates kidney fibrosis in streptozotocin-induced diabetic mice by inhibiting endothelial-to-mesenchymal transition in a therapeutic regimen. Diabetes. 2014;63(6):2120-2131. doi: 10.2337/db13-1029Kanasaki K, Shi S, Kanasaki M, et al. Linagliptin-mediated DPP-4 inhibition ameliorates kidney fibrosis in streptozotocin-induced diabetic mice by inhibiting endothelial-to-mesenchymal transition in a therapeutic regimen. Diabetes. 2014;63(6):2120-2131. doi: 10.2337/db13-1029Dey N, Das F, Mariappan MM, et al. MicroRNA-21 orchestrates high glucose-induced signals to TOR complex 1, resulting in renal cell pathology in diabetes. J Biol Chem. 2011;286(29):25586-25603. doi: 10.1074/jbc.M110.208066Dey N, Das F, Mariappan MM, et al. MicroRNA-21 orchestrates high glucose-induced signals to TOR complex 1, resulting in renal cell pathology in diabetes. J Biol Chem. 2011;286(29):25586-25603. doi: 10.1074/jbc.M110.208066Zhong X, Chung AC, Chen HY, et al. miR-21 is a key therapeutic target for renal injury in a mouse model of type 2 diabetes. Diabetologia. 2013;56(3):663-674. doi: 10.1007/s00125-012-2804-xZhong X, Chung AC, Chen HY, et al. miR-21 is a key therapeutic target for renal injury in a mouse model of type 2 diabetes. Diabetologia. 2013;56(3):663-674. doi: 10.1007/s00125-012-2804-xWang J, Gao Y, Ma M, et al. Effect of miR-21 on renal fibrosis by regulating MMP-9 and TIMP1 in kk-ay diabetic nephropathy mice. Cell Biochem Biophys. 2013;67(2):537-546. doi: 10.1007/s12013-013-9539-2Wang J, Gao Y, Ma M, et al. Effect of miR-21 on renal fibrosis by regulating MMP-9 and TIMP1 in kk-ay diabetic nephropathy mice. Cell Biochem Biophys. 2013;67(2):537-546. doi: 10.1007/s12013-013-9539-2Chau BN, Xin C, Hartner J, et al. MicroRNA-21 promotes fibrosis of the kidney by silencing metabolic pathways. Sci Transl Med. 2012;4(121):121ra118. doi: 10.1126/scitranslmed.3003205Chau BN, Xin C, Hartner J, et al. MicroRNA-21 promotes fibrosis of the kidney by silencing metabolic pathways. Sci Transl Med. 2012;4(121):121ra118. doi: 10.1126/scitranslmed.3003205Wang X, Shen E, Wang Y, et al. Cross talk between miR-214 and PTEN attenuates glomerular hypertrophy under diabetic conditions. Sci Rep. 2016;6:31506. doi: 10.1038/srep31506Wang X, Shen E, Wang Y, et al. Cross talk between miR-214 and PTEN attenuates glomerular hypertrophy under diabetic conditions. Sci Rep. 2016;6:31506. doi: 10.1038/srep31506Zhang Z, Luo X, Ding S, et al. MicroRNA-451 regulates p38 MAPK signaling by targeting of Ywhaz and suppresses the mesangial hypertrophy in early diabetic nephropathy. FEBS Lett. 2012;586(1):20-26. doi: 10.1016/j.febslet.2011.07.042Zhang Z, Luo X, Ding S, et al. MicroRNA-451 regulates p38 MAPK signaling by targeting of Ywhaz and suppresses the mesangial hypertrophy in early diabetic nephropathy. FEBS Lett. 2012;586(1):20-26. doi: 10.1016/j.febslet.2011.07.042Long J, Wang Y, Wang W, et al. Identification of microRNA-93 as a novel regulator of vascular endothelial growth factor in hyperglycemic conditions. J Biol Chem. 2010;285(30):23457-23465. doi: 10.1074/jbc.M110.136168Long J, Wang Y, Wang W, et al. Identification of microRNA-93 as a novel regulator of vascular endothelial growth factor in hyperglycemic conditions. J Biol Chem. 2010;285(30):23457-23465. doi: 10.1074/jbc.M110.136168Tufro A, Veron D. VEGF and podocytes in diabetic nephropathy. Semin Nephrol. 2012;32(4):385-393. doi: 10.1016/j.semnephrol.2012.06.010Tufro A, Veron D. VEGF and podocytes in diabetic nephropathy. Semin Nephrol. 2012;32(4):385-393. doi: 10.1016/j.semnephrol.2012.06.010Fu Y, Zhang Y, Wang Z, et al. Regulation of NADPH oxidase activity is associated with miRNA-25-mediated NOX4 expression in experimental diabetic nephropathy. Am J Nephrol. 2010;32(6):581-589. doi: 10.1159/000322105Fu Y, Zhang Y, Wang Z, et al. Regulation of NADPH oxidase activity is associated with miRNA-25-mediated NOX4 expression in experimental diabetic nephropathy. Am J Nephrol. 2010;32(6):581-589. doi: 10.1159/000322105Feng B, Chen S, McArthur K, et al. miR-146a-Mediated extracellular matrix protein production in chronic diabetes complications. Diabetes. 2011;60(11):2975-2984. doi: 10.2337/db11-0478Feng B, Chen S, McArthur K, et al. miR-146a-Mediated extracellular matrix protein production in chronic diabetes complications. Diabetes. 2011;60(11):2975-2984. doi: 10.2337/db11-0478Muratsu-Ikeda S, Nangaku M, Ikeda Y, et al. Downregulation of miR-205 modulates cell susceptibility to oxidative and endoplasmic reticulum stresses in renal tubular cells. PLoS One. 2012;7(7):e41462. doi: 10.1371/journal.pone.0041462Muratsu-Ikeda S, Nangaku M, Ikeda Y, et al. Downregulation of miR-205 modulates cell susceptibility to oxidative and endoplasmic reticulum stresses in renal tubular cells. PLoS One. 2012;7(7):e41462. doi: 10.1371/journal.pone.0041462Wei J, Zhang Y, Luo Y, et al. Aldose reductase regulates miR-200a-3p/141-3p to coordinate Keap1-Nrf2, Tgfbeta1/2, and Zeb1/2 signaling in renal mesangial cells and the renal cortex of diabetic mice. Free Radic Biol Med. 2014;67:91-102. doi: 10.1016/j.freeradbiomed.2013.10.811Wei J, Zhang Y, Luo Y, et al. Aldose reductase regulates miR-200a-3p/141-3p to coordinate Keap1-Nrf2, Tgfbeta1/2, and Zeb1/2 signaling in renal mesangial cells and the renal cortex of diabetic mice. Free Radic Biol Med. 2014;67:91-102. doi: 10.1016/j.freeradbiomed.2013.10.811Cheng L, Sun X, Scicluna BJ, et al. Characterization and deep sequencing analysis of exosomal and non-exosomal miRNA in human urine. Kidney Int. 2014;86(2):433-444. doi: 10.1038/ki.2013.502Cheng L, Sun X, Scicluna BJ, et al. Characterization and deep sequencing analysis of exosomal and non-exosomal miRNA in human urine. Kidney Int. 2014;86(2):433-444. doi: 10.1038/ki.2013.502Mall C, Rocke DM, Durbin-Johnson B, Weiss RH. Stability of miRNA in human urine supports its biomarker potential. Biomark Med. 2013;7(4):623-631. doi: 10.2217/bmm.13.44Mall C, Rocke DM, Durbin-Johnson B, Weiss RH. Stability of miRNA in human urine supports its biomarker potential. Biomark Med. 2013;7(4):623-631. doi: 10.2217/bmm.13.44Barutta F, Tricarico M, Corbelli A, et al. Urinary exosomal microRNAs in incipient diabetic nephropathy. PLoS One. 2013;8(11):e73798. doi: 10.1371/journal.pone.0073798Barutta F, Tricarico M, Corbelli A, et al. Urinary exosomal microRNAs in incipient diabetic nephropathy. PLoS One. 2013;8(11):e73798. doi: 10.1371/journal.pone.0073798Argyropoulos C, Wang K, McClarty S, et al. Urinary microRNA profiling in the nephropathy of type 1 diabetes. PLoS One. 2013;8(1):e54662. doi: 10.1371/journal.pone.0054662Argyropoulos C, Wang K, McClarty S, et al. Urinary microRNA profiling in the nephropathy of type 1 diabetes. PLoS One. 2013;8(1):e54662. doi: 10.1371/journal.pone.0054662Papadopoulos T, Belliere J, Bascands JL, et al. miRNAs in urine: a mirror image of kidney disease? Expert Rev Mol Diagn. 2015;15(3):361-374. doi: 10.1586/14737159.2015.1009449Papadopoulos T, Belliere J, Bascands JL, et al. miRNAs in urine: a mirror image of kidney disease? Expert Rev Mol Diagn. 2015;15(3):361-374. doi: 10.1586/14737159.2015.1009449Delic D, Eisele C, Schmid R, et al. Urinary Exosomal miRNA Signature in Type II Diabetic Nephropathy Patients. PLoS One. 2016;11(3):e0150154. doi: 10.1371/journal.pone.0150154Delic D, Eisele C, Schmid R, et al. Urinary Exosomal miRNA Signature in Type II Diabetic Nephropathy Patients. PLoS One. 2016;11(3):e0150154. doi: 10.1371/journal.pone.0150154Eissa S, Matboli M, Bekhet MM. Clinical verification of a novel urinary microRNA panal: 133b, -342 and -30 as biomarkers for diabetic nephropathy identified by bioinformatics analysis. Biomed Pharmacother. 2016;83:92-99. doi: 10.1016/j.biopha.2016.06.018Eissa S, Matboli M, Bekhet MM. Clinical verification of a novel urinary microRNA panal: 133b, -342 and -30 as biomarkers for diabetic nephropathy identified by bioinformatics analysis. Biomed Pharmacother. 2016;83:92-99. doi: 10.1016/j.biopha.2016.06.018Liu Y, Gao G, Yang C, et al. Stability of miR-126 in Urine and Its Potential as a Biomarker for Renal Endothelial Injury with Diabetic Nephropathy. Int J Endocrinol. 2014;2014:393109. doi: 10.1155/2014/393109Liu Y, Gao G, Yang C, et al. Stability of miR-126 in Urine and Its Potential as a Biomarker for Renal Endothelial Injury with Diabetic Nephropathy. Int J Endocrinol. 2014;2014:393109. doi: 10.1155/2014/393109DiStefano JK, Taila M, Alvarez ML. Emerging roles for miRNAs in the development, diagnosis, and treatment of diabetic nephropathy. Curr Diab Rep. 2013;13(4):582-591. doi: 10.1007/s11892-013-0386-8DiStefano JK, Taila M, Alvarez ML. Emerging roles for miRNAs in the development, diagnosis, and treatment of diabetic nephropathy. Curr Diab Rep. 2013;13(4):582-591. doi: 10.1007/s11892-013-0386-8Schena FP, Serino G, Sallustio F. MicroRNAs in kidney diseases: new promising biomarkers for diagnosis and monitoring. Nephrol Dial Transplant. 2014;29(4):755-763. doi: 10.1093/ndt/gft223Schena FP, Serino G, Sallustio F. MicroRNAs in kidney diseases: new promising biomarkers for diagnosis and monitoring. Nephrol Dial Transplant. 2014;29(4):755-763. doi: 10.1093/ndt/gft223Long J, Wang Y, Wang W, et al. MicroRNA-29c is a signature microRNA under high glucose conditions that targets Sprouty homolog 1, and its in vivo knockdown prevents progression of diabetic nephropathy. J Biol Chem. 2011;286(13):11837-11848. doi: 10.1074/jbc.M110.194969Long J, Wang Y, Wang W, et al. MicroRNA-29c is a signature microRNA under high glucose conditions that targets Sprouty homolog 1, and its in vivo knockdown prevents progression of diabetic nephropathy. J Biol Chem. 2011;286(13):11837-11848. doi: 10.1074/jbc.M110.194969

The authors declare that there are no conflicts of interest present.