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Journal of Cardiovascular Translational Research

Published in:

01-08-2012

MicroRNAs and Diabetic Complications

Authors: Rama Natarajan, Sumanth Putta, Mitsuo Kato

Published in: Journal of Cardiovascular Translational Research | Issue 4/2012

Abstract

Both Type 1 and Type 2 diabetes can lead to debilitating microvascular complications such as retinopathy, nephropathy and neuropathy, as well as macrovascular complications such as cardiovascular diseases including atherosclerosis and hypertension. Diabetic complications have been attributed to several contributing factors such as hyperglycemia, hyperlipidemia, advanced glycation end products, growth factors, and inflammatory cytokines/chemokines. However, current therapies are not fully efficacious and hence there is an imperative need for a better understanding of the molecular mechanisms underlying diabetic complications in order to identify newer therapeutic targets. microRNAs (miRNAs) are short non-coding RNAs that repress target gene expression via post-transcriptional mechanisms. Emerging evidence shows that they have diverse cellular and biological functions and play key roles in several diseases. In this review, we explore the role of miRNAs in the pathology of diabetic complications and also discuss the potential use of miRNAs as novel diagnostic and therapeutic targets for diabetic complications.

He, Z., & King, G. L. (2004). Microvascular complications of diabetes. Endocrinology and Metabolism Clinics of North America, 33, 215–238. xi-xii.PubMedCrossRef

Beckman, J. A., Creager, M. A., & Libby, P. (2002). Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA, 287, 2570–2581.PubMedCrossRef

Brownlee, M. (2005). The pathobiology of diabetic complications: a unifying mechanism. Diabetes, 54, 1615–1625.PubMedCrossRef

King, G. L., Kunisaki, M., Nishio, Y., Inoguchi, T., Shiba, T., & Xia, P. (1996). Biochemical and molecular mechanisms in the development of diabetic vascular complications. Diabetes, 45(Suppl 3), S105–S108.PubMed

Villeneuve, L. M., Reddy, M. A., & Natarajan, R. (2011). Epigenetics: deciphering its role in diabetes and its chronic complications. Clinical and Experimental Pharmacology and Physiology, 38, 401–409.PubMedCrossRef

Cooper, M. E., & El-Osta, A. (2010). Epigenetics: mechanisms and implications for diabetic complications. Circulation Research, 107, 1403–1413.PubMedCrossRef

Ambros, V. (2004). The functions of animal microRNAs. Nature, 431, 350–355.PubMedCrossRef

Bartel, D. P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116, 281–297.PubMedCrossRef

Bartel, D. P. (2009). MicroRNAs: target recognition and regulatory functions. Cell, 136, 215–233.PubMedCrossRef

10.

Croce, C. M. (2009). Causes and consequences of microRNA dysregulation in cancer. Nature Reviews Genetics, 10, 704–714.PubMedCrossRef

11.

He, L., & Hannon, G. J. (2004). MicroRNAs: small RNAs with a big role in gene regulation. Nature Reviews Genetics, 5, 522–531.PubMedCrossRef

12.

Zamore, P. D., & Haley, B. (2005). Ribo-gnome: the big world of small RNAs. Science, 309, 1519–1524.PubMedCrossRef

13.

Lee, R. C., Feinbaum, R. L., & Ambros, V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 75, 843–854.PubMedCrossRef

14.

Wightman, B., Ha, I., & Ruvkun, G. (1993). Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell, 75, 855–862.PubMedCrossRef

15.

Filipowicz, W., Bhattacharyya, S. N., & Sonenberg, N. (2008). Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nature Reviews Genetics, 9, 102–114.PubMedCrossRef

16.

Stefani, G., & Slack, F. J. (2008). Small non-coding RNAs in animal development. Nature Reviews Molecular Cell Biology, 9, 219–230.PubMedCrossRef

17.

Kim, V. N. (2005). MicroRNA biogenesis: coordinated cropping and dicing. Nature Reviews Molecular Cell Biology, 6, 376–385.PubMedCrossRef

18.

Small, E. M., & Olson, E. N. (2011). Pervasive roles of microRNAs in cardiovascular biology. Nature, 469, 336–342.PubMedCrossRef

19.

Bhatt, K., Mi, Q. S., & Dong, Z. (2011). microRNAs in kidneys: biogenesis, regulation, and pathophysiological roles. American Journal of Physiology. Renal Physiology, 300, F602–F610.PubMedCrossRef

20.

Fernandez-Valverde, S. L., Taft, R. J., & Mattick, J. S. (2011). MicroRNAs in beta-cell biology, insulin resistance, diabetes and its complications. Diabetes, 60, 1825–1831.PubMedCrossRef

21.

Kato, M., Arce, L., & Natarajan, R. (2009). MicroRNAs and their role in progressive kidney diseases. Clinical Journal of the American Society of Nephrology, 4, 1255–1266.PubMedCrossRef

22.

Zhang, C. (2010). MicroRNAs in vascular biology and vascular disease. Journal of Cardiovascular Translational Research, 3, 235–240.PubMedCrossRef

23.

Kempen, J. H., O’Colmain, B. J., Leske, M. C., Haffner, S. M., Klein, R., Moss, S. E., et al. (2004). The prevalence of diabetic retinopathy among adults in the United States. Archives of Ophthalmology, 122, 552–563.PubMedCrossRef

24.

Saaddine, J. B., Honeycutt, A. A., Narayan, K. M., Zhang, X., Klein, R., & Boyle, J. P. (2008). Projection of diabetic retinopathy and other major eye diseases among people with diabetes mellitus: United States, 2005–2050. Archives of Ophthalmology, 126, 1740–1747.PubMedCrossRef

25.

Kovacs, B., Lumayag, S., Cowan, C., & Xu, S. (2011). MicroRNAs in early diabetic retinopathy in streptozotocin-induced diabetic rats. Investigative Ophthalmology & Visual Science, 52, 4402–4409.CrossRef

26.

Feng, B., Chen, S., McArthur, K., Wu, Y., Sen, S., Ding, Q., et al. (2011). miR-146a-Mediated extracellular matrix protein production in chronic diabetes complications. Diabetes, 60, 2975–2984.PubMedCrossRef

27.

McArthur, K., Feng, B., Wu, Y., Chen, S., & Chakrabarti, S. (2011). MicroRNA-200b regulates vascular endothelial growth factor-mediated alterations in diabetic retinopathy. Diabetes, 60, 1314–1323.PubMedCrossRef

28.

Silva, V. A., Polesskaya, A., Sousa, T. A., Correa, V. M., Andre, N. D., Reis, R. I., et al. (2011). Expression and cellular localization of microRNA-29b and RAX, an activator of the RNA-dependent protein kinase (PKR), in the retina of streptozotocin-induced diabetic rats. Molecular Vision, 17, 2228–2240.PubMed

29.

Kato, M., Park, J. T., & Natarajan, R. (2012) MicroRNAs and the glomerulus. Experimental Cell Research, 318, 993–1000.

30.

Ziyadeh, F. N., & Sharma, K. (2003). Overview: combating diabetic nephropathy. Journal of the American Society of Nephrology, 14, 1355–1357.PubMedCrossRef

31.

Kato, M., Zhang, J., Wang, M., Lanting, L., Yuan, H., Rossi, J. J., et al. (2007). MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors. Proceedings of the National Academy of Sciences of the United States of America, 104, 3432–3437.PubMedCrossRef

32.

Sharma, K., & Ziyadeh, F. N. (1995). Hyperglycemia and diabetic kidney disease. The case for transforming growth factor-beta as a key mediator. Diabetes, 44, 1139–1146.PubMedCrossRef

33.

Yamamoto, T., Nakamura, T., Noble, N. A., Ruoslahti, E., & Border, W. A. (1993). Expression of transforming growth factor beta is elevated in human and experimental diabetic nephropathy. Proceedings of the National Academy of Sciences of the United States of America, 90, 1814–1818.PubMedCrossRef

34.

Kato, M., Wang, L., Putta, S., Wang, M., Yuan, H., Sun, G., et al. (2010). Post-transcriptional up-regulation of Tsc-22 by Ybx1, a target of miR-216a, mediates TGF-{beta}-induced collagen expression in kidney cells. Journal of Biological Chemistry, 285, 34004–34015.PubMedCrossRef

35.

Kato, M., Arce, L., Wang, M., Putta, S., Lanting, L., & Natarajan, R. (2011). A microRNA circuit mediates transforming growth factor-beta1 autoregulation in renal glomerular mesangial cells. Kidney International, 80, 358–368.PubMedCrossRef

36.

Kato, M., Putta, S., Wang, M., Yuan, H., Lanting, L., Nair, I., et al. (2009). TGF-beta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN. Nature Cell Biology, 11, 881–889.PubMedCrossRef

37.

Kato, M., & Natarajan, R. (2009). microRNA cascade in diabetic kidney disease: big impact initiated by a small RNA. Cell Cycle, 8, 3613–3614.PubMedCrossRef

38.

Wang, Q., Wang, Y., Minto, A. W., Wang, J., Shi, Q., Li, X., et al. (2008). MicroRNA-377 is up-regulated and can lead to increased fibronectin production in diabetic nephropathy. The FASEB Journal, 22, 4126–4135.CrossRef

39.

Wang, X. X., Jiang, T., Shen, Y., Caldas, Y., Miyazaki-Anzai, S., Santamaria, H., et al. (2010). Diabetic nephropathy is accelerated by farnesoid X receptor deficiency and inhibited by farnesoid X receptor activation in a type 1 diabetes model. Diabetes, 59, 2916–2927.PubMedCrossRef

40.

Long, J., Wang, Y., Wang, W., Chang, B. H., & Danesh, F. R. (2010). Identification of microRNA-93 as a novel regulator of vascular endothelial growth factor in hyperglycemic conditions. Journal of Biological Chemistry, 285, 23457–23465.PubMedCrossRef

41.

Long, J., Wang, Y., Wang, W., Chang, B. H., & Danesh, F. R. (2011). 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. Journal of Biological Chemistry, 286, 11837–11848.PubMedCrossRef

42.

Wang, B., Komers, R., Carew, R., Winbanks, C. E., Xu, B., Herman-Edelstein, M., et al. (2012). Suppression of microRNA-29 expression by TGF-beta1 promotes collagen expression and renal fibrosis. Journal of the American Society of Nephrology, 23, 252–265.PubMedCrossRef

43.

Krupa, A., Jenkins, R., Luo, D. D., Lewis, A., Phillips, A., & Fraser, D. (2010). Loss of MicroRNA-192 promotes fibrogenesis in diabetic nephropathy. Journal of the American Society of Nephrology, 21, 438–447.PubMedCrossRef

44.

Wang, B., Herman-Edelstein, M., Koh, P., Burns, W., Jandeleit-Dahm, K., Watson, A., et al. (2010). E-cadherin expression is regulated by miR-192/215 by a mechanism that is independent of the profibrotic effects of transforming growth factor-beta. Diabetes, 59, 1794–1802.PubMedCrossRef

45.

Wang, B., Koh, P., Winbanks, C., Coughlan, M. T., McClelland, A., Watson, A., et al. (2011). miR-200a Prevents renal fibrogenesis through repression of TGF-beta2 expression. Diabetes, 60, 280–287.PubMedCrossRef

46.

Dey, N., Das, F., Mariappan, M. M., Mandal, C. C., Ghosh-Choudhury, N., Kasinath, B. S., et al. (2011). MicroRNA-21 orchestrates high glucose-induced signals to TOR complex 1, resulting in renal cell pathology in diabetes. Journal of Biological Chemistry, 286, 25586–25603.PubMedCrossRef

47.

Zhang, Z., Peng, H., Chen, J., Chen, X., Han, F., Xu, X., et al. (2009). MicroRNA-21 protects from mesangial cell proliferation induced by diabetic nephropathy in db/db mice. FEBS Letters, 583, 2009–2014.PubMedCrossRef

48.

Fu, Y., Zhang, Y., Wang, Z., Wang, L., Wei, X., Zhang, B., et al. (2010). Regulation of NADPH oxidase activity is associated with miRNA-25-mediated NOX4 expression in experimental diabetic nephropathy. American Journal of Nephrology, 32, 581–589.PubMedCrossRef

49.

Caporali, A., Meloni, M., Vollenkle, C., Bonci, D., Sala-Newby, G. B., Addis, R., et al. (2010). Deregulation of microRNA-503 contributes to diabetes mellitus-induced impairment of endothelial function and reparative angiogenesis after limb ischemia. Circulation, 123, 282–291.CrossRef

50.

Natarajan, R., & Nadler, J. L. (2004). Lipid inflammatory mediators in diabetic vascular disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 24, 1542–1548.PubMedCrossRef

51.

Brownlee, M. (2001). Biochemistry and molecular cell biology of diabetic complications. Nature, 414, 813–820.PubMedCrossRef

52.

Devaraj, S., Dasu, M. R., & Jialal, I. (2010). Diabetes is a proinflammatory state: a translational perspective. Expert Review of Endocrinology and Metabolism, 5, 19–28.PubMed

53.

Libby, P., Ridker, P. M., & Maseri, A. (2002). Inflammation and atherosclerosis. Circulation, 105, 1135–1143.PubMedCrossRef

54.

Shan, Z. X., Lin, Q. X., Deng, C. Y., Zhu, J. N., Mai, L. P., Liu, J. L., et al. (2010). miR-1/miR-206 regulate Hsp60 expression contributing to glucose-mediated apoptosis in cardiomyocytes. FEBS Letters, 584, 3592–3600.PubMedCrossRef

55.

Katare, R., Caporali, A., Zentilin, L., Avolio, E., Sala-Newby, G., Oikawa, A., et al. (2011). Intravenous gene therapy with PIM-1 via a cardiotropic viral vector halts the progression of diabetic cardiomyopathy through promotion of prosurvival signaling. Circulation Research, 108, 1238–1251.PubMedCrossRef

56.

Wang, X. H., Qian, R. Z., Zhang, W., Chen, S. F., Jin, H. M., & Hu, R. M. (2009). MicroRNA-320 expression in myocardial microvascular endothelial cells and its relationship with insulin-like growth factor-1 in type 2 diabetic rats. Clinical and Experimental Pharmacology and Physiology, 36, 181–188.PubMedCrossRef

57.

Care, A., Catalucci, D., Felicetti, F., Bonci, D., Addario, A., Gallo, P., et al. (2007). MicroRNA-133 controls cardiac hypertrophy. Nature Medicine, 13, 613–618.PubMedCrossRef

58.

Feng, B., Chen, S., George, B., Feng, Q., & Chakrabarti, S. (2010). miR133a regulates cardiomyocyte hypertrophy in diabetes. Diabetes/Metabolism Research and Reviews, 26, 40–49.PubMedCrossRef

59.

Shen, E., Diao, X., Wang, X., Chen, R., & Hu, B. (2011). MicroRNAs involved in the mitogen-activated protein kinase cascades pathway during glucose-induced cardiomyocyte hypertrophy. American Journal of Pathology, 179, 639–650.PubMedCrossRef

60.

Greco, S., Fasanaro, P., Castelvecchio, S., D’Alessandra, Y., Arcelli, D., Di Donato, M., et al. (2012). MicroRNA dysregulation in diabetic ischemic heart failure patients. Diabetes (in press).

61.

van Rooij, E., Sutherland, L. B., Liu, N., Williams, A. H., McAnally, J., Gerard, R. D., et al. (2006). A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proceedings of the National Academy of Sciences of the United States of America, 103, 18255–18260.PubMedCrossRef

62.

Duisters, R. F., Tijsen, A. J., Schroen, B., Leenders, J. J., Lentink, V., van der Made, I., et al. (2009). miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling. Circulation Research, 104, 170–178. 176p following 178.PubMedCrossRef

63.

Thum, T., Gross, C., Fiedler, J., Fischer, T., Kissler, S., Bussen, M., et al. (2008). MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature, 456, 980–984.PubMedCrossRef

64.

Reddy, M. A., & Natarajan, R. (2011). Epigenetic mechanisms in diabetic vascular complications. Cardiovascular Research, 90, 421–429.PubMedCrossRef

65.

Shanmugam, N., Reddy, M. A., & Natarajan, R. (2008). Distinct roles of heterogeneous nuclear ribonuclear protein K and microRNA-16 in cyclooxygenase-2 RNA stability induced by S100b, a ligand of the receptor for advanced glycation end products. Journal of Biological Chemistry, 283, 36221–36233.PubMedCrossRef

66.

Villeneuve, L. M., Reddy, M. A., Lanting, L. L., Wang, M., Meng, L., & Natarajan, R. (2008). Epigenetic histone H3 lysine 9 methylation in metabolic memory and inflammatory phenotype of vascular smooth muscle cells in diabetes. Proceedings of the National Academy of Sciences of the United States of America, 105, 9047–9052.PubMedCrossRef

67.

Villeneuve, L. M., Kato, M., Reddy, M. A., Wang, M., Lanting, L., & Natarajan, R. (2010). Enhanced levels of microRNA-125b in vascular smooth muscle cells of diabetic db/db mice lead to increased inflammatory gene expression by targeting the histone methyltransferase Suv39h1. Diabetes, 59, 2904–2915.PubMedCrossRef

68.

Reddy, M. A., Jin, W., Villeneuve, L., Wang, M., Lanting, L., Todorov, I., et al. (2012). Pro-inflammatory role of MicroRNA-200 in vascular smooth muscle cells from diabetic mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 32, 721–729.PubMedCrossRef

69.

Jin, W., Reddy, M. A., Chen, Z., Putta, S., Lanting, L., Kato, M., et al. (2012). Small RNA sequencing reveals microRNAs that modulate angiotensin II effects in vascular smooth muscle cells. Journal of Biological Chemistry (in press).

70.

Thomas, M. C., Groop, P. H., & Tryggvason, K. (2012). Towards understanding the inherited susceptibility for nephropathy in diabetes. Current Opinion in Nephrology and Hypertension, 21, 195–202.PubMedCrossRef

71.

Bruno, A. E., Li, L., Kalabus, J. L., Pan, Y., Yu, A., & Hu, Z. (2012). miRdSNP: a database of disease-associated SNPs and microRNA target sites on 3′UTRs of human genes. BMC Genomics, 13, 44.PubMedCrossRef

72.

Sun, G., Yan, J., Noltner, K., Feng, J., Li, H., Sarkis, D. A., et al. (2009). SNPs in human miRNA genes affect biogenesis and function. RNA, 15, 1640–1651.PubMedCrossRef

73.

Miao, F., Chen, Z., Zhang, L., Liu, Z., Wu, X., Yuan, Y. C. et al. (2012). Profiles of epigenetic histone post-translational modifications at type 1 diabetes susceptible genes. Journal of Biological Chemistry (in press).

74.

Sapienza, C., Lee, J., Powell, J., Erinle, O., Yafai, F., Reichert, J., et al. (2011). DNA methylation profiling identifies epigenetic differences between diabetes patients with ESRD and diabetes patients without nephropathy. Epigenetics, 6, 20–28.PubMedCrossRef

75.

Farazi, T. A., Spitzer, J. I., Morozov, P., & Tuschl, T. (2011). miRNAs in human cancer. The Journal of Pathology, 223, 102–115.PubMedCrossRef

76.

Fabbri, M. (2010). miRNAs as molecular biomarkers of cancer. Expert Review of Molecular Diagnostics, 10, 435–444.PubMedCrossRef

77.

Wang, K., Zhang, S., Marzolf, B., Troisch, P., Brightman, A., Hu, Z., et al. (2009). Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proceedings of the National Academy of Sciences of the United States of America, 106, 4402–4407.PubMedCrossRef

78.

Mitchell, P. S., Parkin, R. K., Kroh, E. M., Fritz, B. R., Wyman, S. K., Pogosova-Agadjanyan, E. L., et al. (2008). Circulating microRNAs as stable blood-based markers for cancer detection. Proceedings of the National Academy of Sciences of the United States of America, 105, 10513–10518.PubMedCrossRef

79.

Tijsen, A. J., Creemers, E. E., Moerland, P. D., de Windt, L. J., van der Wal, A. C., Kok, W. E., et al. (2010). MiR423-5p as a circulating biomarker for heart failure. Circulation Research, 106, 1035–1039.PubMedCrossRef

80.

Wang, G., Kwan, B. C., Lai, F. M., Chow, K. M., Kam-Tao Li, P., & Szeto, C. C. (2010). Expression of microRNAs in the urinary sediment of patients with IgA nephropathy. Disease Markers, 28, 79–86.PubMed

81.

Neal, C. S., Michael, M. Z., Pimlott, L. K., Yong, T. Y., Li, J. Y., & Gleadle, J. M. (2011). Circulating microRNA expression is reduced in chronic kidney disease. Nephrology, Dialysis, Transplantation, 26, 3794–3802.PubMedCrossRef

82.

Starkey Lewis, P. J., Dear, J., Platt, V., Simpson, K. J., Craig, D. G., Antoine, D. J., et al. (2011). Circulating microRNAs as potential markers of human drug-induced liver injury. Hepatology, 54, 1767–1776.PubMedCrossRef

83.

Elmen, J., Lindow, M., Schutz, S., Lawrence, M., Petri, A., Obad, S., et al. (2008). LNA-mediated microRNA silencing in non-human primates. Nature, 452, 896–899.PubMedCrossRef

84.

Krutzfeldt, J., Rajewsky, N., Braich, R., Rajeev, K. G., Tuschl, T., Manoharan, M., et al. (2005). Silencing of microRNAs in vivo with ‘antagomirs’. Nature, 438, 685–689.PubMedCrossRef

85.

Putta, S., Lanting, L., Sun, G., Lawson, G., Kato, M., & Natarajan, R. (2012). Inhibiting microRNA-192 ameliorates renal fibrosis in diabetic nephropathy. Journal of the American Society of Nephrology, 23, 458–469.PubMedCrossRef

86.

Sun, L., Zhang, D., Liu, F., Xiang, X., Ling, G., Xiao, L., et al. (2011). Low-dose paclitaxel ameliorates fibrosis in the remnant kidney model by down-regulating miR-192. The Journal of Pathology, 225, 364–377.PubMedCrossRef

87.

Snove, O., Jr., & Rossi, J. J. (2006). Expressing short hairpin RNAs in vivo. Nature Methods, 3, 689–695.PubMedCrossRef

88.

Ebert, M. S., Neilson, J. R., & Sharp, P. A. (2007). MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nature Methods, 4, 721–726.PubMedCrossRef

89.

Chung, A. C., Huang, X. R., Meng, X., & Lan, H. Y. (2010). miR-192 mediates TGF-beta/Smad3-driven renal fibrosis. Journal of the American Society of Nephrology, 21, 1317–1325.PubMedCrossRef

Title: MicroRNAs and Diabetic Complications
Authors: Rama Natarajan
Sumanth Putta
Mitsuo Kato
Publication date: 01-08-2012
Publisher: Springer US
Published in: Journal of Cardiovascular Translational Research / Issue 4/2012
Print ISSN: 1937-5387
Electronic ISSN: 1937-5395
DOI: https://doi.org/10.1007/s12265-012-9368-5

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