VEGF and Podocytes in Diabetic Nephropathy

Seminars in Nephrology

Volumn 32, Issue 4, 2012, Pages 385-393

  Tufro, Alda ^a   Veron, Delma ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Diabetes mellitus; Diabetic nephropathy complications; Endothelial nitric oxide synthase(eNOS); Reactive oxygen species (ROS); VEGF receptor 2 (VEGFR2); VEGF A

Indexed keywords

ADVANCED GLYCATION END PRODUCT; NEPHRIN; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; PHOSPHATIDYLINOSITOL 3 KINASE; REACTIVE OXYGEN METABOLITE; VASCULOTROPIN; VASCULOTROPIN A; VASCULOTROPIN RECEPTOR 2;

ALBUMINURIA; APOPTOSIS; ARTICLE; AUTOCRINE EFFECT; CELL SHAPE; DIABETES MELLITUS; DIABETIC NEPHROPATHY; ENDOTHELIUM CELL; EXTRACELLULAR MATRIX; GLOMERULUS BASEMENT MEMBRANE; HUMAN; HYPERGLYCEMIA; MESANGIUM CELL; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; PODOCYTE; PRIORITY JOURNAL; PROTEINURIA; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; SIGNAL TRANSDUCTION;

ANIMALS; CELL SURVIVAL; DIABETIC NEPHROPATHIES; GLYCOSYLATION END PRODUCTS, ADVANCED; HUMANS; NITROGEN OXIDES; PODOCYTES; RENIN-ANGIOTENSIN SYSTEM; SIGNAL TRANSDUCTION; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84865709126     PISSN: 02709295     EISSN: 15584488     Source Type: Journal    
DOI: 10.1016/j.semnephrol.2012.06.010     Document Type: Article

References (121)

1. Leung D.W., Cachianes G., Kuang W.J., Goeddel D.V., Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989, 246:1306-1309.
2. Keck P.J., Hauser S.D., Krivi G., Sanzo K., Warren T., Feder J., et al. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 1989, 246:1309-1312.
3. Senger D.R. Vascular endothelial growth factor: much more than an angiogenesis factor. Mol Biol Cell 2010, 21:377-379.
4. Coultas L., Chawengsaksophak K., Rossant J. Endothelial cells and VEGF in vascular development. Nature 2005, 438:937-945.
5. Ferrara N., Carver-Moore K., Chen H., Dowd M., Lu L., O'Shea K.S., et al. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 1996, 380:439-442.
6. Shalaby F., Rossant J., Yamaguchi T.P., Gertsenstein M., Wu X.F., Breitman M.L., et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 1995, 376:62-66.
7. Fong G.H., Rossant J., Gertsenstein M., Breitman M.L. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 1995, 376:66-70.
8. Weis S.M., Cheresh D.A. Pathophysiological consequences of VEGF-induced vascular permeability. Nature 2005, 437. 497-04.
9. USRDS 2008 annual data report US Renal Data System, Accessed 2009. http://www.usrds.org.
10. Rossing K., Christensen P.K., Hovind P., Parving H.H. Remission of nephrotic-range albuminuria reduces risk of end-stage renal disease and improves survival in type 2 diabetic patients. Diabetologia 2005, 48:2241-2247.
11. Hovind P., Tarnow L., Rossing P., Carstensen B., Parving H.H. Improved survival in patients obtaining remission of nephrotic range albuminuria in diabetic nephropathy. Kidney Int 2004, 66:1180-1186.
12. Hovind P., Tarnow L., Rossing K., Rossing P., Eising S., Larsen N., et al. Decreasing incidence of severe diabetic microangiopathy in type 1 diabetes. Diabetes Care 2003, 26:1258-1264.
13. McKnight A.J., Maxwell A.P., Patterson C.C., Brady H.R., Savage D.A. Association of VEGF-1499C→T polymorphism with diabetic nephropathy in type 1 diabetes mellitus. J Diab Compl 2007, 21:242-245.
14. Simon M., Grone H.J., Johren O., Kullmer J., Plate K.H., Risau W., et al. Expression of vascular endothelial growth factor and its receptors in human renal ontogenesis and in adult kidney. Am J Physiol Renal Fluid Electrolyte Physiol 1995, 268:F240-F250.
15. Tufro A., Norwood V.F., Carey R.M., Gomez R.A. Vascular endothelial growth factor induces nephrogenesis, and vasculogenesis. J Am Soc Nephrol 1999, 10:2125-2134.
16. Guan F., Villegas G., Teichman J., Mundel P., Tufro A. Autocrine VEGF-A system in podocytes regulates podocin and its interaction with CD2AP. Am J Physiol Renal Physiol 2006, 291:F422-F428.
17. Cui T., Foster R.R., Saleem M., Mathieson P.W., Gillatt D.A., Bates D.O., et al. Differentiated human podocytes endogenously express an inhibitory isoform of vascular endothelial growth factor (VEGF165b) mRNA and protein. Am J Physiol Renal Physiol 2004, 286:F767-F773.
18. Villegas G., Lange-Sperandio G.B., Tufro A. Autocrine and paracrine functions of vascular endothelial growth factor (VEGF) in renal tubular epithelial cells. Kidney Int 2005, 67:449-457.
19. Kanellis J., Fraser S., Katerelos M., Power D.A. Vascular endothelial growth factor is a survival factor for renal tubular epithelial cells. Am J Physiol Renal Physiol 2000, 278:F905-F915.
20. Kim B.S., Chen J., Weinstein T., Noiri E., Goligorsky M.S. VEGF expression in hypoxia and hyperglycemia: reciprocal effect on branching angiogenesis in epithelial-endothelial co-cultures. J Am Soc Nephrol 2002, 8:2027-2036.
21. Tufro A. VEGF spatially directs angiogenesis during metanephric development in vitro. Dev Biol 2000, 227:558-566.
22. Eremina V., Sood M., Haigh J., Nagy A., Lajoie G., Ferrara N., et al. Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases. J Clin Invest 2003, 111:707-716.
23. Roberts W.G., Palade G.E. Neovasculature induced by vascular endothelial growth factor is fenestrated. Cancer Res 1997, 757:765-772.
24. Kamba T., Tam B.Y., Hashizume H., et al. VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol 2006, 290:H560-H576.
25. Eremina V., Cui S., Gerber H., Ferrara N., Haigh J., Nagy A., et al. Vascular endothelial growth factor a signaling in the podocyte-endothelial compartment is required for mesangial cell migration and survival. J Am Soc Nephrol 2006, 17:724-735.
26. Veron D., Reidy K., Villegas G., Kopp J., Thomas D., Tufro A. Induction of podocyte VEGF-A overexpression in adult mice causes glomerular disease. Kidney Int 2010, 77:989-999.
27. Veron D., Reidy K., Marlier A., Villegas G., Kashgarian M., Tufro A. Induction of podocyte VEGF164 overexpression at different stages of development causes congenital nephrosis or steroid resistant nephrotic syndrome. Am J Pathol 2010, 177:2225-2233.
28. Tervaert T.W., Mooyaart A.L., Amann K., Society R.P., et al. Pathologic classification of diabetic nephropathy. J Am Soc Nephrol 2010, 21:556-563.
29. Eremina V., Jefferson J.A., Kowalewska J., Hochster H., Haas M., Weisstuch J., et al. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 2008, 358:1129-1136.
30. 3 integrin signaling in the glomerulus. PLoS One 2012, 7:e40589. Epub 2012 Jul 13.
31. Foster R.R., Saleem M.A., Mathieson P.W., Bates D.O., Harper S.J. Vascular endothelial growth factor and nephrin interact and reduce apoptosis in human podocytes. Am J Physiol Renal Physiol 2005, 288:F48-F57.
32. Müller-Deile J., Worthmann K., Saleem M., Tossidou I., Haller H., Schiffer M. The balance of autocrine VEGF-A and VEGF-C determines podocyte survival. Am J Physiol Renal Physiol 2009, 297:F1656-F1667.
33. Gerber H.P., McMurtrey A., Kowalski J., Yan M., Keyt B.A., Dixit V., et al. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J Biol Chem 1998, 273:30336-30343.
34. Lee S., Chen T.T., Barber C.L., Jordan M.C., Murdock J., Desai S., et al. Autocrine VEGF signaling is required for vascular homeostasis. Cell 2007, 130:691-703.
35. Ku C.H., White K.E., Dei Cas A., Hayward A., Webster Z., Bilous R., et al. Inducible overexpression of sFlt-1 in podocytes ameliorates glomerulopathy in diabetic mice. Diabetes 2008, 57:2824-2833.
36. Huber T.B., Hartleben B., Kim J., Schmidts M., Schermer B., Keil A., et al. Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling. Mol Cell Biol 2003, 23:4917-4928.
37. Bertuccio C., Veron D., Aggarwal P., Holzman L., Tufro A. Vascular endothelial growth factor receptor 2 direct interaction with nephrin links VEGF-A signals to actin in kidney podocytes. J Biol Chem 2011, 286:39933-39944.
38. Sison K., Eremina V., Baelde H., Min W., Hirashima M., Fantus I.G., et al. Glomerular structure and function require paracrine, not autocrine, VEGF-VEGFR-2 signaling. J Am Soc Nephrol 2010, 21:1691-1701.
39. Turlo K.A., Gallaher S.D., Vora R., Laski F.A., Iruela-Arispe M.L. When Cre-mediates recombination does not result in protein loss. Genetics 2010, 186:959-967.
40. 164) overexpression causes severe nodular glomerulosclerosis in a mouse model of type 1 diabetes. Diabetologia 2011, 54:1227-1241.
41. Faul C., Asanuma K., Yanagida-Asanuma E., Kimand K., Mundel P. Actin up: regulation of podocyte structure and function by components of the actin cytoskeleton. Trends Cell Biol 2007, 17:428-437.
42. Saleem M.A., Zavadil J., Bailly M., McGee K., Witherden I.R., Pavenstadt H., et al. The molecular and functional phenotype of glomerular podocytes reveals key features of contractile smooth muscle cells. Am J Physiol Renal Physiol 2008, 295:F959-F970.
43. Mele C., Iatropoulos P., Donadelli R., Calabria A., Maranta R., Cassis P., et al. MYO1E mutations and childhood familial focal segmental glomerulosclerosis. N Engl J Med 2011, 365:295-306.
44. Matsukawa M., Sakamoto H., Kawasuji M., Furuyama T., Ogawa M. Different roles of Foxo1 and Foxo3 in the control of endothelial cell morphology. Genes Cells 2009, 14:1167-1181.
45. Strilić B., Kucera T., Eglinger J., Hughes M.R., McNagny K.M., Tsukita S., et al. The molecular basis of vascular lumen formation in the developing mouse aorta. Dev Cell 2009, 17:505-515.
46. Neufeld G., Cohen T., Gengrinovitch S., Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 1999, 13:9-22.
47. Waltenberger J., Claesson-Welsh L., Siegbahn A., Shibuya M., Heldin C.H. Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. J Biol Chem 1994, 269:26988-26995.
48. Takahashi T., Yamaguchi S., Chida K., Shibuya M. A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-gamma and DNA synthesis in vascular endothelial cells. EMBO J 2001, 20:2768-2778.
49. Quack I., Woznowski M., Potthoff S.A., Palmer R., Königshausen E., Sivritas S., et al. PKC alpha mediates beta-arrestin2-dependent nephrin endocytosis in hyperglycemia. J Biol Chem 2011, 286:12959-12970.
50. Tossidou I., Teng B., Menne J., Shushakova N., Park J.K., Becker J.U., et al. Podocytic PKC-alpha is regulated in murine and human diabetes and mediates nephrin endocytosis. PLoS One 2010, 5:e10185.
51. Rask-Madsen C., King G.L. Differential regulation of VEGF signaling by PKC-alpha and PKC-epsilon in endothelial cells. Arterioscler Thromb Vasc Biol 2008, 28:919-924.
52. Hovind P., Tarnow L., Oestergaard P.B., Parving H.H. Elevated vascular endothelial growth factor in type 1 diabetic patients with diabetic nephropathy. Kidney Int 2000, 75:S56-S61.
53. Chiarelli F., Spagnoli A., Basciani F., Tumini S., Mezzetti A., Cipollone F., et al. Vascular endothelial growth factor (VEGF) in children, adolescents and young adults with type 1 diabetes mellitus: relation to glycaemic control and microvascular complications. Diabet Med 2000, 17:650-656.
54. Stieger N., Worthmann K., Schiffer M. The role of metabolic and haemodynamic factors in podocyte injury in diabetes. Diabetes Metab Res Rev 2011, 27:207-215.
55. Shulman K., Rosen S., Tognazzi K., Manseau E.J., Brown L.F. Expression of vascular permeability factor (VPF/VEGF) is altered in many glomerular diseases. J Am Soc Nephrol 1996, 7:661-666.
56. Hohenstein B., Hausknecht B., Boehmer K., Riess R., Brekken R.A., Hugo C.P. Local VEGF activity but not VEGF expression is tightly regulated during diabetic nephropathy in man. Kidney Int 2006, 69:1654-1661.
57. Brosius F.C., Alpers C.E., Bottinger E.P., et al. Animal models of diabetic complications consortium. Mouse models of diabetic nephropathy. J Am Soc Nephrol 2009, 20:2503-2512.
58. Brosius F.C., Khoury C.C., Buller C.L., Chen S. Abnormalities in signaling pathways in diabetic nephropathy. Expert Rev Endocrinol Metab 2010, 5:51-64.
59. Kim N.H., Kim K.B., Kim D.L., Kim S.G., Choi K.M., Baik S.H., et al. Plasma and urinary vascular endothelial growth factor and diabetic nephropathy in type 2 diabetes mellitus. Diabet Med 2004, 21:545-551.
60. Cooper M.E., Vranes D., Youssef S., Stacker S.A., Cox A.J., Rizkalla B., et al. Increased renal expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 in experimental diabetes. Diabetes 1999, 48:2229-2239.
61. Gurley S.B., Coffman T.M. The renin-angiotensin system and diabetic nephropathy. Semin Nephrol 2007, 27:144-152.
62. Wolf G., Ziyadeh F.N. Cellular and molecular mechanisms of proteinuria in diabetic nephropathy. Nephron Physiol 2007, 106:26-31.
63. Kakoki M., Sullivan K.A., Backus C., Hayes J.M., Oh S.S., Hua K., et al. Lack of both bradykinin B1 and B2 receptors enhances nephropathy, neuropathy, and bone mineral loss in Akita diabetic mice. Proc Natl Acad Sci U S A 2010, 107:10190-10195.
64. Sanchez de Miguel L., Neysari S., Jakob S., Petrimpol M., Butz N., Banfi A., et al. B2-kinin receptor plays a key role in B1-, angiotensin converting enzyme inhibitor-, and vascular endothelial growth factor-stimulated in vitro angiogenesis in the hypoxic mouse heart. Cardiovasc Res 2008, 80:106-113.
65. Thuringer D., Maulon L., Frelin C. Rapid transactivation of the vascular endothelial growth factor receptor KDR/Flk-1 by the bradykinin B2 receptor contributes to endothelial nitric-oxide synthase activation in cardiac capillary endothelial cells. J Biol Chem 2002, 277:2028-2032.
66. Rigat B., Hubert C., Alhenc-Gelas F., et al. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990, 86:1343-1346.
67. Bodin S., Chollet C., Goncalves-Mendes N., et al. Kallikrein protects against microalbuminuria in experimental type I diabetes. Kidney Int 2009, 76:395-403.
68. Tikellis C., Bialkowski K., Pete J., Sheehy K., Su Q., Johnston C., et al. ACE2 deficiency modifies renoprotection afforded by ACE inhibition in experimental diabetes. Diabetes 2008, 57:1018-1025.
69. Liu C.X., Hu Q., Wang Y., Zhang W., Ma Z.Y., Feng J.B., et al. Angiotensin-converting enzyme (ACE) 2 overexpression ameliorates glomerular injury in a rat model of diabetic nephropathy: a comparison with ACE inhibition. Mol Med 2011, 17:59-69.
70. Dröge W. Free radicals in the physiological control of cell function. Physiol Rev 2002, 82:47-95.
71. Johansen J.S., Harris A.K., Rychly D.J., Ergul A. Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovasc Diabetol 2005, 4:5.
72. Lin C.L., Wang F.S., Hsu Y.C., Chen C.N., Tseng M.J., Saleem M.A., et al. Modulation of notch-1 signaling alleviates vascular endothelial growth factor-mediated diabetic nephropathy. Diabetes 2010, 59:1915-1925.
73. Richard D.E., Berra E., Pouyssegur J. Nonhypoxic pathway mediates the induction of hypoxia-inducible factor 1alpha in vascular smooth muscle cells. J Biol Chem 2000, 275:26765-26771.
74. Papapetropoulos A., Garcia-Cardena G., Madri J.A., Sessa W.C. Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. J Clin Invest 1997, 100:3131-3139.
75. Tsurumi Y., Murohara T., Krasinski K., Chen D., Witzenbichler B., Kearney M., et al. Reciprocal relation between VEGF and NO in the regulation of endothelial integrity. Nat Med 1997, 3:879-886.
76. Gao N., Ding M., Zheng J.Z., Zhang Z., Leonard S.S., Liu K.J., et al. Vanadate-induced expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor through phosphatidylinositol 3-kinase/Akt pathway and reactive oxygen species. J Biol Chem 2002, 277:31963-31971.
77. Nakagawa T. Uncoupling of VEGF with NO as a mechanism for diabetic nephropathy. Diabetes Res Clin Pract 2008, 82(Suppl 1):S67-S69.
78. Karalliedde J., Gnudi L. Endothelial factors and diabetic nephropathy. Diabetes Care 2011, 34(Suppl 2):S291-S296.
79. Nakagawa T., Kosugi T., Haneda M., Rivard C.J., Long D.A. Abnormal angiogenesis in diabetic nephropathy. Diabetes 2009, 58:1471-1478.
80. Nakagawa T., Sato W., Glushakova O., Heinig M., Clarke T., Campbell-Thompson M., et al. Diabetic endothelial nitric oxide synthase knockout mice develop advanced diabetic nephropathy. J Am Soc Nephrol 2007, 18:539-550.
81. Zhao H.J., Wang S., Cheng H., Zhang M.Z., Takahashi T., Fogo A.B., et al. Endothelial nitric oxide synthase deficiency produces accelerated nephropathy in diabetic mice. J Am Soc Nephrol 2006, 17:2664-2669.
82. Wang C.H., Li F., Hiller S., Kim H.S., Maeda N., Smithies O., et al. A modest decrease in endothelial NOS in mice comparable to that associated with human NOS3 variants exacerbates diabetic nephropathy. Proc Natl Acad Sci U S A 2011, 108:2070-2075.
83. Ezzidi I., Mtiraoui N., Mohamed M.B., Mahjoub T., Kacem M., Almawi W.Y. Association of endothelial nitric oxide synthase Glu298Asp, 4b/a, and -786T>C gene variants with diabetic nephropathy. J Diabetes Complications 2008, 22:331-338.
84. Forbes M.S., Thornhill B.A., Park M.H., Chevalier R.L. Lack of endothelial nitric-oxide synthase leads to progressive focal renal injury. Am J Pathol 2007, 170:87-99.
85. Tan A.L., Forbes J.M., Cooper M.E. AGE, RAGE, and ROS in diabetic nephropathy. Semin Nephrol 2007, 27:130-143.
86. Tsuchida K., Makita Z., Yamagishi S., Atsumi T., Miyoshi H., Obara S., et al. Suppression of transforming growth factor beta and vascular endothelial growth factor in diabetic nephropathy in rats by a novel advanced glycation end product inhibitor, OPB-9195. Diabetologia 1999, 42:579-588.
87. Wendt T.M., Tanji N., Guo J., Kislinger T.R., Qu W., Lu Y., et al. RAGE drives the development of glomerulosclerosis and implicates podocyte activation in the pathogenesis of diabetic nephropathy. Am J Pathol 2003, 162:1123-1137.
88. Tanji N., Markowitz G.S., Fu C., Kislinger T., Taguchi A., Pischetsrieder M., et al. Expression of advanced glycation end products and their cellular receptor RAGE in diabetic nephropathy and nondiabetic renal disease. J Am Soc Nephrol 2000, 11:1656-1666.
89. Bierhaus A., Humpert P.M., Morcos M., Wendt T., Chavakis T., Arnold B., et al. Understanding RAGE, the receptor for advanced glycation end products. J Mol Med (Berl) 2005, 83:876-886.
90. Thallas-Bonke V., Thorpe S.R., Coughlan M.T., Fukami K., Yap F.Y., Sourris K.C., et al. Inhibition of NADPH oxidase prevents advanced glycation end product-mediated damage in diabetic nephropathy through a protein kinase C-alpha-dependent pathway. Diabetes 2008, 57:460-469.
91. Myint K.M., Yamamoto Y., Doi T., Kato I., Harashima A., Yonekura H., et al. RAGE control of diabetic nephropathy in a mouse model: effects of RAGE gene disruption and administration of low-molecular weight heparin. Diabetes 2006, 55:2510-2522.
92. Liu H., Luo Y., Zhang T., Zhang Y., Wu Q., Yuan L., et al. Genetic deficiency of aldose reductase counteracts the development of diabetic nephropathy in C57BL/6 mice. Diabetologia 2011, 54:1242-1251.
93. Fioretto P., Mauer M. Histopathology of diabetic nephropathy. Semin Nephrol 2007, 27:195-207.
94. Wu L., Derynck R. Essential role of TGF-beta signaling in glucose-induced cell hypertrophy. Dev Cell 2009, 17:35-48.
95. de Vriese A.S., Tilton R.G., Elger M., Stephan C.C., Kriz W., Lameire N.H. Antibodies against vascular endothelial growth factor improve early renal dysfunction in experimental diabetes. J Am Soc Nephrol 2001, 12:993-1000.
96. Flyvbjerg A., Dagnaes-Hansen F., De Vriese A.S., Schrijvers B.F., Tilton R.G., Rasch R. Amelioration of long-term renal changes in obese type 2 diabetic mice by a neutralizing vascular endothelial growth factor antibody. Diabetes 2002, 51:3090-3094.
97. Veron D., Garcia A.M., Reidy K., Tufro A. VEGF-A dysregulation alters the glomerular phenotype of streptozotocin diabetic mice. J Am Soc Nephrol 2008, 19:405A.
98. Gavard J., Gutkind J.S. VEGF controls endothelial-cell permeability by promoting the beta-arrestin-dependent endocytosis of VE-cadherin. Nat Cell Biol 2006, 8:1223-1234.
99. Suzuki H., Usui I., Kato I., Oya T., Kanatani Y., Yamazaki Y., et al. Deletion of platelet-derived growth factor receptor-β improves diabetic nephropathy in Ca(2+)/calmodulin-dependent protein kinase IIα (Thr286Asp) transgenic mice. Diabetologia 2011, 54:2953-2962.
100. Hanahan D. Signaling vascular morphogenesis and maintenance. Science 1997, 277:48-50.
101. Tapia R., Guan F., Gershin I., Teichman J., Villegas G., Tufro A. Semaphorin3a disrupts podocyte foot processes causing acute proteinuria. Kidney Int 2008, 73:733-740.
102. Reidy K.J., Villegas G., Veron D., Jimenez J., Thomas D., Tufro A. Semaphorin3a regulates endothelial cell number and podocyte differentiation during glomerular development. Development 2009, 136:3979-3989.
103. Jeansson M., Gawlik A., Anderson G., Li C., Kerjaschki D., Henkelman M., et al. Angiopoietin-1 is essential in mouse vasculature during development and in response to injury. J Clin Invest 2011, 121:2278-2289.
104. Sung S.H., Ziyadeh F.N., Wang A., Pyagay P.E., Kanwar Y.S., Chen S. Blockade of vascular endothelial growth factor signaling ameliorates diabetic albuminuria in mice. J Am Soc Nephrol 2006, 17:3093-3104.
105. Zhang S.X., Wang J.J., Lu K., Mott R., Longeras R., Ma J.X. Therapeutic potential of angiostatin in diabetic nephropathy. J Am Soc Nephrol 2006, 17:475-486.
106. Yamamoto Y., Maeshima Y., Kitayama H., Kitamura S., Takazawa Y., Sugiyama H., et al. Tumstatin peptide, an inhibitor of angiogenesis, prevents glomerular hypertrophy in the early stage of diabetic nephropathy. Diabetes 2004, 53:1831-1840.
107. Ichinose K., Maeshima Y., Yamamoto Y., Kitayama H., Takazawa Y., Hirokoshi K., et al. Antiangiogenic endostatin peptide ameliorates renal alterations in the early stage of a type 1 diabetic nephropathy model. Diabetes 2005, 54:2891-2903.
108. Rask-Madsen C., King G.L. Diabetes: podocytes lose their footing. Nature 2010, 468:42-44.
109. Thomas S., Vanuystel J., Gruden G., Rodríguez V., Burt D., Gnudi L., et al. Vascular endothelial growth factor receptors in human mesangium in vitro and in glomerular disease. J Am Soc Nephrol 2000, 11:1236-1243.
110. Iglesias-de la Cruz M.C., Ziyadeh F.N., Isono M., Kouahou M., Han D.C., Kalluri R. Effects of high glucose and TGF-beta1 on the expression of collagen IV and vascular endothelial growth factor in mouse podocytes. Kidney Int 2002, 62:901-913.
111. Wang Y., Fei D., Vanderlaan M., Song A. Biological activity of bevacizumab, a humanized anti-VEGF antibody in vitro. Angiogenesis 2004, 7:335-345.
112. Tahara A., Tsukada J., Tomura Y., Yatsu T., Shibasaki M. Vasopressin regulates rat mesangial cell growth by inducing autocrine secretion of vascular endothelial growth factor. J Physiol Sci 2011, 61:115-122.
113. Kanwar Y.S., Sun L., Xie P., Liu F.Y., Chen S. A glimpse of various pathogenetic mechanisms of diabetic nephropathy. Annu Rev Pathol 2011, 6:395-423.
114. Rooney B., O'Donovan H., Gaffney A., Browne M., Faherty N., Curran S.P., et al. CTGF/CCN2 activates canonical Wnt signalling in mesangial cells through LRP6: implications for the pathogenesis of diabetic nephropathy. FEBS Lett 2011, 585:531-538.
115. Suzuma K., Naruse K., Suzuma I., Takahara N., Ueki K., Aiello L.P., et al. Vascular endothelial growth factor induces expression of connective tissue growth factor via KDR, Flt1, and phosphatidylinositol 3-kinase-akt-dependent pathways in retinal vascular cells. J Biol Chem 2000, 275:40725-40731.
116. Inoki I., Shiomi T., Hashimoto G., Enomoto H., Nakamura H., Makino K., et al. Connective tissue growth factor binds vascular endothelial growth factor (VEGF) and inhibits VEGF-induced angiogenesis. FASEB J 2002, 16:219-221.
117. Hashimoto G., Inoki I., Fujii Y., Aoki T., Ikeda E., Okada Y. Matrix metalloproteinases cleave connective tissue growth factor and reactivate angiogenic activity of vascular endothelial growth factor 165. J Biol Chem 2002, 277:36288-36295.
118. Keil A., Blom I.E., Goldschmeding R., Rupprecht H.D. Nitric oxide down-regulates connective tissue growth factor in rat mesangial cells. Kidney Int 2002, 62:401-411.
119. Hakroush S., Moeller M.J., Theilig F., Kaissling B., Sijmonsma T.P., Jugold M., et al. Effects of increased renal tubular vascular endothelial growth factor (VEGF) on fibrosis, cyst formation, and glomerular disease. Am J Pathol 2009, 175:1883-1895.
120. Welsh G.I., Hale L.J., Eremina V., Jeansson M., Maezawa Y., Lennon R., et al. Insulin signaling to the glomerular podocyte is critical for normal kidney function. Cell Metab 2010, 12:329-340.
121. Wang Y., Heilig K., Saunders T., Minto A., Deb D.K., Chang A., et al. Transgenic overexpression of GLUT1 in mouse glomeruli produces renal disease resembling diabetic glomerulosclerosis.s. Am J Physiol Renal Physiol 2010, 299:F99-F111.