Download PDF
Horm Metab Res 2009; 41(8): 585-593
DOI: 10.1055/s-0029-1220752
Review

© Georg Thieme Verlag KG Stuttgart · New York

Role of Growth Factors in Diabetic Kidney Disease

F. Chiarelli 1 , S. Gaspari 1 , M. L. Marcovecchio 1
  • 1Department of Paediatrics, University of Chieti, Chieti, Italy
Further Information

Publication History

Publication Date:
18 May 2009 (online)

Also available at
    Permissions and Reprints

Abstract

Diabetic nephropathy (DN) is one of the major microvascular complications of diabetes and one of the leading causes of death among patients with diabetes. DN is characterized by excessive amassing of extracellular matrix with thickening of glomerular and tubular basement membranes and increased amount of mesangial matrix, which ultimately progress to glomerulosclerosis and tubulo-interstitial fibrosis. The high intracellular glucose environment due to an increased cellular uptake of glucose activates several pathways related to the production of advanced glycation endproducts, cytokines, chemokines, growth factors, reactive oxidative species, which are all final mediators of renal damage in human and experimental diabetes. Several growth factors have been implicated in the pathogenesis of DN, through complex intra-renal systems. Transforming growth factor beta, connective tissue growth factor, vascular endothelial growth factor, growth hormone and insulin-like growth factors are among those best known and investigated. There are also data, even though limited, on the involvement of other two growth factors, epidermal growth factor and platelet derived growth factor, in the pathogenesis of DN. These growth factors, which are generally expressed in the normal kidney and whose levels increase in relation to diabetes, have been implicated in the control of renal matrix composition, cell hypertrophy, proliferation and survival, modulation of cells of the immune system, and enzymes involved in glucose metabolism. The development of specific inhibitors of growth factors has provided further evidence for the involvement of growth factors in the development and progression of DN and further studies might help in developing new potential therapeutical interventions.

Key words

diabetic nephropathy - type 1 diabetes mellitus - growth factors

References

  • 1 World Health Organization. .Diabetes: World Health Organization Fact Sheet. Geneva: World Health Organization 2006: 1-2 (no. 312)
  • 2 Russel TA. Diabetic Nephropathy in patients with type 1 diabetes mellitus.  Nephrol Nurs J. 2006;  33 15-28
    Google Scholar
  • 3 , US Renal Data system: annual Data Report 2005. Available: http://www.usrds.org/adr.htm
  • 4 Van Dijk PC, Jager KJ, Stengel B, Gronhagen-Riska C, Feest TG, Briggs JD. Renal replacement therapy for diabetic end-stage renal disease: data from 10 registries in Europe (1991–2000).  Kidney Int. 2005;  67 1489-1499
    Google Scholar
  • 5 Rossing P. Prediction, progression and prevention of diabetic nephropathy. The Minkowski Lecture 2005.  Diabetologia. 2006;  49 11-19
    Google Scholar
  • 6 Bogdanović R. Diabetic nephropathy in children and adolescents.  Pediatr Nephrol. 2008;  23 507-255
    Google Scholar
  • 7 Cooper ME. Interaction of metabolic and haemodynamic factors in mediating experimental diabetic nephropathy.  Diabetologia. 2001;  44 1957-1972
    Google Scholar
  • 8 Osterby R. Glomerular structural changes in type 1 (insulin-dependent) diabetes mellitus: causes, consequences, and prevention.  Diabetologia. 1992;  35 803-812
    Google Scholar
  • 9 Chiarelli F, Santilli F, Mohn A. Role of growth factors in the development of diabetic complications.  Horm Res. 2000;  53 53-67
    Google Scholar
  • 10 Navarro JF, Mora-Fernandez. The role of TNF-α nephropathy: Pathogenic and therapeutic implications.  Cytokine Growth Factor Rev. 2006;  17 441-450
    Google Scholar
  • 11 Reeves WB, Andreoli TE. Transforming Growth Factor-β contributes to progressive diabetic nephropathy.  Proc Natl Acad Sci U S A. 2000;  97 7667-7669
    Google Scholar
  • 12 Tsuchida KI, Cronin B, Sharma K. Novel aspects of transforming growth factor-beta in diabetic kidney disease.  Nephron. 2002;  92 7-21
    Google Scholar
  • 13 Reddy AS. Diabetic Nephropathy: Theory & practise. East Hanover, NJ: College Book Publishers. L.L.C. 2004: 563
  • 14 Monkawa T, Hiromura K, Wolf G, Shankland SJ. The hypertrophic effect of transforming growth factor-beta is reduced in the absence of cyclin-dependent kinase-inhibitors p21 and p27.  J Am Soc Nephrol. 2002;  13 1172-1178
    Google Scholar
  • 15 Chen S, Jim B, Ziyadeh FN. Diabetic nephropathy and transforming Growth Factor-β: Transforming our view of glomerulosclerosis and fibrosis build-up.  Semin Nephol. 2003;  23 532-543
    Google Scholar
  • 16 Ziyadeh FN, Sharma K. Role of transforming growth factor-beta in diabetic glomerulosclerosis and renal hypertrophy.  Kidney Int. 1995;  51 S34-S36
    Google Scholar
  • 17 Yamagishi SI, Inagaki Y, Okamoto T. Advanced glycation end products inhibit de novo protein synthesis and induce TGF-beta overexpression in proximal tubular cells.  Kidney Int. 2003;  63 464-473
    Google Scholar
  • 18 Kang MJ, Ingram A, Ly H, Thai K, Scholey JW. Effects of diabetes and hypertension on glomerular transforming growth factor-beta receptor expression.  Kidney Int. 2000;  58 1677-1685
    Google Scholar
  • 19 Wang S, Skorczewski J, Feng X, Mei L, Murphy-Ullrich JE. Glucose up-regulates thrombospondin 1 gene transcription and transforming growth factor-beta activity through antagonism of cGMP-dependent protein kinase repression via upstream stimulatory factor 2.  J Biol Chem. 2004;  279 34311-34322
    Google Scholar
  • 20 Lawrence DA. Transforming growth factor-beta: a general review.  Eur Cytokine Netw. 1996;  7 363-374
    Google Scholar
  • 21 Ribeiro SM, Poczatek M, Schultz-Cherry S, Villain M, Murphy-Ullrich JE. The activation sequence of thrombospondin-1 interacts with the latency-associated peptide to regulate activation of latent transforming growth factor-beta.  J Biol Chem. 1999;  274 13586-13593
    Google Scholar
  • 22 Yevdokimova N, Wahab NA, Mason RM. Thrombospondin-1 is the key activator of TGF-beta1 in human mesangial cells exposed to high glucose.  J Am Soc Nephrol. 2001;  12 703-712
    Google Scholar
  • 23 Yung S, Lee CY, Zhang Q, Lau SK, Tsang RC, Chan TM. Elevated glucose induction of thrombospondin-1 up-regulates fibronectin synthesis in proximal renal tubular epithelial cells through TGF-beta1 dependent and TGF-beta1 independent pathways.  Nephrol Dial Transplant. 2006;  21 1504-1513
    Google Scholar
  • 24 Daniel C, Schaub K, Amann K, Lawler J, Hugo C. Thrombospondin-1 is an endogenous activator of TGF-beta in experimental diabetic nephropathy in vivo.  Diabetes. 2007;  56 2982-2989
    Google Scholar
  • 25 Reeves WB, Andreoli TE. Transforming Growth Factor-β contributes to progressive diabetic nephropathy.  Proc Natl Acad Sci USA. 2000;  97 7667-7669
    Google Scholar
  • 26 Sharma K, Eltayeb BO, McGowan TA, Dunn SR, Alzahabi B, Rohde R, Ziyadeh FN, Lewis EJ. Captopril-induced reduction of serum levels of transforming growth factor-beta1 correlates with long-term renoprotection in insulin-dependent diabetic patients.  Am J Kidney Dis. 1999;  34 818-823
    Google Scholar
  • 27 Ohtomo S, Izuhara Y, Takizawa S, Yamada N, Kakuta T, van Ypersele de Strihou C, Miyata T. Thiazolidinediones provide better renoprotection that insulin in a obese, hypertensive type II diabetic rat model.  Kidney Int. 2007;  72 1512-1519
    Google Scholar
  • 28 Lang F, Klingel K, Wagner CA, Stegen C, Warntges S, Friedrich B, Lanzendorfer M, Melzig J, Moschen I, Steuer S, Waldegger S, Sauter M, Paulmichl M, Gerke V, Risler T, Gamba G, Capasso G, Kandolf R, Hebert SC, Massry SG, Broër S. Deranged transcriptional regulation of cell-volume-sensitive kinase hSGK in diabetic nephropathy.  Proc Natl Acad Sci USA. 2000;  97 8157-8162
    Google Scholar
  • 29 Korpinem E, Teppo AM, Hukkanem L, Akerblom HK, Gronhagen-Riska C, Vaarala O. Urinary Transforming Growth Factor-β1 and 1-Microglobulin Children and Adolescents With Type 1 Diabetes.  Diabetes Care. 2000;  23 664-668
    Google Scholar
  • 30 Han DC, Isono M, Hoffman BB, Ziyadeh FN. High glucose stimulates proliferation and collagen type 1 synthesis in renal cortical fibroblasts: mediation by autocrine activation of TGF-β1.  J Am Soc Nephrol. 1999;  10 1891-1899
    Google Scholar
  • 31 Sharma K, Jin Y, Guo J, Ziyadeh FN. Neutralization of TGF-beta by anti-TGF-beta antibody attenuates kidney hypertrophy and the enhanced extracellular matrix gene expression in STZ-induced diabetic mice.  Diabetes. 1996;  45 522-530
    Google Scholar
  • 32 Kulkarni AB, Ward JM, Yaswen L, Mackall CL, Bauer SR, Huh CG, Gress RE, Karlsson S. Transforming growth factor-beta 1 null mice.  An animal model for inflammatory disorders. Am J Pathol. 1995;  146 264-275
    Google Scholar
  • 33 Wang S, Hirscheberg R. BMP-7 antagonizes TGF-beta-dependent fibrogenesis in mesangial cells.  Am J Physiol Renal Pysiol. 2003;  284 1006-1013
    Google Scholar
  • 34 Guha M, Xu ZG, Tung D, Lanting L, Natarajan R. Specific down-regulation of connective tissue growth factor attenuates progression of nephropathy in mouse models of type 1 and type 2 diabetes.  FASEB J. 2007;  21 3355-3368
    Google Scholar
  • 35 Riser BL, Denichilo M, Cortes P, Baker C, Grondin JM, Yee J, Narins RG. Regulation of connective tissue growth factor activity in cultured rat mesangial cells and its expression in experimental diabetic glomerulosclerosis.  J Am Soc Nephrol. 2000;  11 25-38
    Google Scholar
  • 36 Sakharova OV, Taal MW, Brenner BM. Pathogenesis of diabetic nephropathy: focus on transforming growth factor-beta and connective tissue growth factor.  Curr Opin Nephrol Hypertens. 2001;  10 727-738
    Google Scholar
  • 37 Wahab NA, Yevdokimova N, Weston BS, Roberts T, Li XJ, Brinkman H, Mason RM. Role of connective tissue growth factor in the pathogenesis of diabetic nephropathy.  Biochem J. 2001;  359 77-87
    Google Scholar
  • 38 Hishikawa K, Oemar BS, Nakaki T. Static pressure regulates connective tissue growth factor expression in human mesangial cells.  J Biol Chem. 2001;  276 16797-16803
    Google Scholar
  • 39 Twigg SM, Chen MM, Joly AH, Chakrapani SD, Tsubaki J, Kim HS, Oh Y, Rosenfeld RG. Advanced glycosylation end products up-regulate connective tissue growth factor (insulin-like growth factor-binding protein-related protein 2) in human fibroblasts: a potential mechanism for expansion of extracellular matrix in diabetes mellitus.  Endocrinology. 2001;  142 1760-1769
    Google Scholar
  • 40 Wang S, Denichilo M, Brubaker C, Hirschberg R. Connective tissue growth factor in tubulointerstitial injury of diabetic nephropathy.  Kidney Int. 2001;  60 96-105
    Google Scholar
  • 41 Burns W, Twigg S, Forbes J, Pete J, Tikellis C, Thallas-Bonke V, Thomas MC, Cooper ME, Kantharidis P. Connective Tissue Growth Factor plays an important role in advanced glycation end product-induced tubular epithelial-to-mesenchymal transition: implications for diabetic renal disease.  J Am Soc Nephrol. 2006;  17 2484-2494
    Google Scholar
  • 42 Kobayashi T, Inoue T, Okada H, Kikuta T, Kanno Y, Nishida T, Takigawa M, Sugaya T, Suzuki H. Connective tissue growth factor mediates the profibrotic effects of transforming growth factor-β produced by tubular epithelial cells in response to high glucose.  Clin Exp Nephrol. 2005;  9 114-121
    Google Scholar
  • 43 Roestenberg P, van Nieuwenhoven FA, Joles JA, Trischberger C, Martens PP, Oliver N, Aten J, Hoppener JW, Goldschmeding R. Temporal expression profile and distribution pattern indicate a role of connective tissue growth factor (CTGF/CCN-2) in diabetic nephropathy in mice.  Am J Physiol Renal Physiol. 2006;  290 F1344-F1354
    Google Scholar
  • 44 Gilbert RE, Akdeniz A, Weitz S, Usinger WR, Molineaux C, Jones SE, Langham RG, jerums G. Urinary connective tissue growth factor excretion in patients with type 1 diabetes and nephropathy.  Diabetes Care. 2003;  26 2632-2636
    Google Scholar
  • 45 Riser BL, Cortes P, deNichilo M, Deshmukh PV, Chahal PS, Mohammed AK, Yee J, Kahkonem D. Urinary CCN2 as a possible predictor of diabetic nephropathy: preliminary report.  Kidney Int. 2003;  64 451-458
    Google Scholar
  • 46 Nguyen TQ, Tarnow L, Jorsal A, Oliver N, Roestenberg P, Ito Y, Parving HH, Rossing P, van Nieuwenhoven FA, Goldschmeding R. Plasma connective tissue growth factor is an independent predictor of end-stage renal disease and mortality in type 1 diabetic nephropathy.  Diabetes Care. 2008;  31 1177-1182
    Google Scholar
  • 47 Nguyen TQ, Tarnow L, Andersen S, Hovind P, Parving HH, Goldschmeding R, van nieuwenhoven FA. Urinary connective tissue growth factor excretion correlates with clinical markers of renal disease in a large population of type 1 diabetic patients with diabetic nephropathy.  Diabetes Care. 2006;  29 83-88
    Google Scholar
  • 48 Guha M, Xu ZG, Tung D, Lanting L, Natarajan R. Specific down-regulation of connective tissue growth factor attenuates progression of nephropathy in mouse models of type 1 and type 2 diabetes.  FASEB J. 2007;  21 3355-3368
    Google Scholar
  • 49 Khamaisi M, Schrijvers BF, DeVriese AS, Raz I, Flyvbjerg A. The emerging role of VEGF in diabetic kidney disease.  Nephrol Dial Transplant. 2003;  18 1427-1430
    Google Scholar
  • 50 De Vriese AS, Tilton RG, Elger M, Stephan C, Kriz W, Lameire NH. Antibodies against Vascular Endothelial Growth Factor Improve Early Renal Dysfunction in Experimental Diabetes.  J Am Soc Nephrol. 2001;  12 993-1000
    Google Scholar
  • 51 Chiarelli F, Spagnoli A, Basciani F, Tumini S, Mezzetti A, Cipollone F, Cuccurullo F, Morgese G, Verrotti A. Vascular endothelial growth factor (VEGF) in children, adolescents and young adults with Type 1 diabetes mellitus: relation to glycaemic control and microvascular complications.  Diabetes. 2000;  17 650-656
    Google Scholar
  • 52 Cooper ME, Vranes D, Youssef S, Stacker SA, Cox AJ, Rizkalla B, Casley DJ, Bach LA, Kelly DJ, Gilbert RE. Increased renal expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 in experimental diabetes.  Diabetes. 1999;  48 2229-2239
    Google Scholar
  • 53 Chiarelli F, de Martino M, Mezzetti A, Catino M, Morgese G, Cuccurullo F, Verrotti A. Advanced glycation end products in children and adolescents with diabetes: relation to glycemic control and early microvascular complications.  J Pediatr. 1999;  134 486-491
    Google Scholar
  • 54 Santilli F, Spagnoli A, Mohn A, Tumini S, Verrotti A, Cipollone F, Mezzetti A, Chiarelli F. Increased vascular endothelial growth factor serum concentrations may help to identify patients with onset of type 1 diabetes during childhood at risk for developing persistent microalbuminuria.  J Clin Endocrinol Metab. 2001;  86 3871-3876
    Google Scholar
  • 55 Senthil D, Choudhury GG, McLaurin C, Kasinath BB. Vascular endothelial growth factor induces protein synthesis in renal epithelial cells: A potential role in diabetic nephropathy.  Kidney Int. 2003;  64 468-479
    Google Scholar
  • 56 Ziche M, Morbidelli L, Choudhuri R, Zhang HT, Donnini S, Granger HJ, Bicknell R. Nitric oxide synthase lies downstream from vascular endothelial growth factor-induced but not basic fibroblast growth factor-induced angiogenesis.  J Clin Invest. 1997;  99 2625-2634
    Google Scholar
  • 57 Hood JD, Meininger CJ, Ziche M, Granger HJ. VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells.  Am J Physiol. 1998;  274 H1054-H1058
    Google Scholar
  • 58 Iglesias de la Cruz MC, Ziyadeh FN, Isono M, Kouahou M, Han DC, Kalluri R, Mundel P, Chen S. Effects of high glucose and TGF-β on the expression of collagen IV and vascular endothelial growth factor in mouse podocytes.  Kidney Int. 2002;  62 901-913
    Google Scholar
  • 59 Iozzo RV. Heparan sulphate proteoglycans: intricate molecules with intriguing functions.  J Clin Invest. 2001;  108 165-167
    Google Scholar
  • 60 Gabbai FB, Blantz RC. Role of nitric oxide in renal hemodynamics.  Semin Nephrol. 1999;  19 242-250
    Google Scholar
  • 61 Baelde HJ, Eikmans M, Lappin DWP, Doran PP, Hohenadel D, Brinkkoetter P-T, van der Woude FJ, Waldherr R, Rabelink TJ, de Heer E, Bruijn JA. Reduction of VEGF-A and CTGF expression in diabetic nephropathy is associated with podocyte loss.  Kidney Int. 2007;  71 637-645
    Google Scholar
  • 62 Dalla VM, Masiero A, Roiter AM. Is podocyte injury relevant in diabetic nephropathy? Studies in patients with type 2 diabetes.  Diabetes. 2003;  52 1031-1035
    Google Scholar
  • 63 Susztak K, Raff AC, Schiffer M, Bottinger EP. Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy.  Diabetes. 2006;  55 225-233
    Google Scholar
  • 64 Coward RJM, Welsh GI, Yang J, Tasman C, Lennon R, Koziell A, Satchell S, Holman GD, Kerjaschki D, Tavaré JM, Mathieson PW, Saleem MA. The human glomerular podocyte is a novel target for insulin action.  Diabetes. 2005;  54 3095-3102
    Google Scholar
  • 65 Durvasula RV, Shankland SJ. Mechanical strain increases SPARC levels in podocytes implications for glomerulosclerosis.  Am J Physiol Renal Physiol. 2005;  289 E577-F584
    Google Scholar
  • 66 Cooper ME, Thomas MC. Interactions between growth factors in the kidney: implications for progressive renal injury.  Kidney Int. 2003;  63 1584-1585
    Google Scholar
  • 67 Dunger DB, Acerini CL. IGF-I and diabetes in adolescence.  Diabetes Metab. 1998;  24 101-107
    Google Scholar
  • 68 Dunger DB, Cheetham TD. Growth hormone insulin-like growth factor I axis in insulin-dependent diabetes mellitus.  Horm Res. 1996;  46 2-6
    Google Scholar
  • 69 Vasylyeva TL, Ferry RJ. Novel roles of the IGF-IGFBP axis in etiopathophysiology of diabetic nephropathy.  Diabetes Res Clin Pract. 2007;  76 177-186
    Google Scholar
  • 70 Rabkin R, Schaefer F. New concepts: growth hormone, insulin-like growth factor-I and the kidney.  Growth Horm IGF Res. 2004;  14 270-276
    Google Scholar
  • 71 Moller J. Effects of growth hormone on fluid homeostasis. Clinical and experimental aspects.  Growth Horm IGF Res. 2003;  13 55-74
    Google Scholar
  • 72 Ferry Jr RJ, Cohen P. The insulin-like growth factor axis in pediatrics.  Clin Pediatr Endocrinol. 1999;  8 1-10
    Google Scholar
  • 73 Han HJ, Kang CW, Park SH. Tissue-specific regulation of insulin-like growth factors and insulin- like growth factors binding proteins in male diabetic rats in vivo and in vitro.  Clin Exp Pharmacol Physiol. 2006;  33 1172-1179
    Google Scholar
  • 74 Wędrychowicz A, Dziatkowiak H, Nazim J, Sztefko K. Insulin-Like Growth Factor-1 and Its Binding Proteins, IGFBP-1 and IGFBP-3, in Adolescents with Type-1 Diabetes mellitus and Microalbuminuria.  Horm Res. 2005;  63 245-251
    Google Scholar
  • 75 Reiter EO, Rosenfeld RG. IGFs and its binding proteins. In: Greenspan F, Strewler G, ed. Basic and Clinical Endocrinology. East Norwalk, CT: Appleton & Lange 1997: 1437-1453
    Google Scholar
  • 76 Cummings EA, Sochett EB, Dekker MG, Lawson ML, Daneman D. Contribution of growth hormone and IGF-I to early diabetic nephropathy in type 1 diabetes.  Diabetes. 1998;  47 1341-1346
    Google Scholar
  • 77 Amin R, Schultz C, Ong K, Frystyk J, Dalton RN, Perrv E, Orskov H, Dunger DB. Low IGF-I and elevated testosterone during puberty in subjects with type 1 diabetes developing microalbuminuria in comparison to normoalbuminuric control subjects.  Diabetes Care. 2003;  26 1456-1461
    Google Scholar
  • 78 Bereket A, Lang CH, Wilson TA. Alterations in the growth hormone-insulin-like growth factor axis in insulin dependent diabetes mellitus.  Horm Metab Res. 1999;  31 172-181
    Google Scholar
  • 79 Niedzwiedzka A, Dziatkowiak H, Sztefko K. Insulin-like growth factor I (IGF-I) and its binding proteins 1 and 3 in children and adolescents with IDDM.  Horm Res. 1999;  5l ((Suppl 2)) 95
    Google Scholar
  • 80 Shinada M, Akdeniz A, Panagiotopoulos S, Jerums G, Bach LA. Proteolysis of insulin-like growth factor-binding protein-3 is increased in urine from patients with diabetic nephropathy.  J Clin Endocrinol Metab. 2000;  85 1163-1169
    Google Scholar
  • 81 Vasylyeva TL, Chen X, Ferry RJ. Insulin-like growth factor-binding protein-3 mediates cytokine-induced mesangial cell apoptosis.  Growth Horm IGF Res. 2005;  15 207-214
    Google Scholar
  • 82 Landau D, Segey Y, Afargan M. A novel somatostatin analogue prevents early renal complications in the nonobese diabetic mouse.  Kidney Int. 2001;  60 505-512
    Google Scholar
  • 83 Flyvbjerg A. Potential use of growth hormone receptor antagonist in the treatment of diabetic kidney disease.  Growth Horm IGF Res. 2001;  11 S115-S119
    Google Scholar
  • 84 Segev Y, Landau D, Rasch R, Flyvbjerg A, Phillip M. Growth hormone receptor antagonism prevents early renal changes in nonobese diabetic mice.  J Am Soc Nephrol. 1999;  10 2374-2381
    Google Scholar
  • 85 Abboud HE. Role of platelet-derived growth factor in renal injury.  Annu Rev Physiol. 1995;  57 297-309
    Google Scholar
  • 86 Fagerudd JA, Groop PH, Honkanen E, Teppo AM, Gronhagen-Riska C. Urinary excretion of TGF-beta 1, PDGF-BB and fibronectin in insulin-dependent diabetes mellitus patients.  Kidney Int Suppl. 1997;  63 S195-S197
    Google Scholar
  • 87 Nakagawa H, Sasahara M, Haneda M, Koya D, Hazama F, Kikkawa R. Immunohistochemical characterization of glomerular PDGF B-chain and PDGF beta-receptor expression in diabetic rats.  Diabetes Res Clin Pract. 2000;  48 87-98
    Google Scholar
  • 88 Soyombo AA, DiCorleto PE. Stable expression of human platelet-derived growth factor B chain by bovine aortic endothelial cells. Matrix association and selective proteolytic cleavage by thrombin.  J Biol Chem. 1994;  269 17734-17740
    Google Scholar
  • 89 Langham RG, Kelly DJ, Maguire J, Dowling JP, Gilbert RE, Thomson NM. Over-expression of platelet-derived growth factor in human diabetic nephropathy.  Nephrol Dial Transplant. 2003;  18 1392-1396
    Google Scholar
  • 90 Uehara G, Suzuki D, Toyoda M, Umezono T, Sakai H. Glomerular expression of platelet-derived growth factor (PDGF)-A,-B chain and PDGF receptor-alpha, -beta in human diabetic nephropathy.  Clin Exp Nephrol. 2004;  8 36-42
    Google Scholar
  • 91 Eitner F, Bücher E, van Roeyen C, Kunter U, Rong S, Seikrit C, Villa L, Boor P, Fredriksson L, Bäckström G, Eriksson U, Ostman A, Floege J, Ostendorf T. PDGF-C is a proinflammatory cytokine that mediates renal interstitial fibrosis.  J Am Soc Nephrol. 2008;  19 281-289
    Google Scholar
  • 92 Gilbert RE, Cox A, MacNally PG, Wu LL, Dziadek M, Cooper ME, Jerums G. Increased epidermal growth factor in experimental diabetes related kidney growth in rats.  Diabetologia. 1997;  40 778-785
    Google Scholar
  • 93 Kanda S, Igawa T, Sakai H, Nomata K, Kanetake H, Saito Y. Anti-epidermal growth factor antibody inhibits compensatory renal hyperplasia but not hypertrophy after unilateral nephrectomy in mice.  Biochem Biophys Res Commun. 1992;  187 1015-1021
    Google Scholar
  • 94 Stevens VA, Saad S, Chen XM, Pollock CA. The interdependence of EGF-R and SGK-1 in fibronectin expression in primary kidney cortical fibroblast cells.  Intern J Biochem Cell Biol. 2007;  39 1047-1054
    Google Scholar
  • 95 Feng Y, Wang Q, Wang Y, Yard B, Lang F. SGK1 mediated fibronectin formation in diabetic nephropathy.  Cell Physiol Biochem. 2005;  16 237-244
    Google Scholar
  • 96 Yun CC. Concerted roles of SGK1 and the Na+-H+ exchanger regulatory factor 2 (NHERF2) in regulation of NHE3.  Cell Physiol Biochem. 2003;  13 29-40
    Google Scholar
  • 97 Warntges S, Grone HJ, Capasso G. Cell volume regulatory mechanisms in progression of renal disease.  J Nephrol. 2001;  14 319-326
    Google Scholar
  • 98 Wassef L, Kelly DJ, Gilbert RE. Epidermal growth factor receptor inhibition attenuates early kidney enlargement in experimental diabetes.  Kidney Int. 2004;  66 1805-1814
    Google Scholar

Correspondence

F. ChiarelliMD, PhD 

Department of Pediatrics

University of Chieti

Via dei Vestini 5

66100 Chieti

Italy

Phone: +39/0871/35 80 15

Fax: +39/0871/57 48 31

Email: chiarelli@unich.it