Transforming growth factor-beta and the kidney: What we know and what we can do?

Current Enzyme Inhibition

Volumn 6, Issue 2, 2010, Pages 87-96

  Yang, Hai Chun ^a   Zuo, Yiqin ^a   Fogo, Agnes B ^a  

^a VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Fibrosis; Kidney; TGF

Indexed keywords

ACTIVIN RECEPTOR LIKE KINASE 1; ALPHAVBETA6 INTEGRIN; ANGIOTENSIN 1 RECEPTOR ANTAGONIST; ANGIOTENSIN II; BONE MORPHOGENETIC PROTEIN; CONNECTIVE TISSUE GROWTH FACTOR; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENDOGLIN; MATRIX METALLOPROTEINASE; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PLASMINOGEN ACTIVATOR INHIBITOR 1; PROTEIN KINASE C; THROMBOSPONDIN; THYMOSIN BETA4; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA RECEPTOR; TRANSFORMING GROWTH FACTOR BETA1; TRANSFORMING GROWTH FACTOR BETA2; TRANSFORMING GROWTH FACTOR BETA3;

ANIMAL; ARTICLE; CHRONIC ALLOGRAFT NEPHROPATHY; EPITHELIAL MESENCHYMAL TRANSITION; FOCAL GLOMERULOSCLEROSIS; GENE EXPRESSION; GENE OVEREXPRESSION; GENETIC POLYMORPHISM; GLOMERULONEPHRITIS; GLOMERULUS; HUMAN; HYPERTENSION; IMMUNOMODULATION; KIDNEY; KIDNEY DISEASE; KIDNEY FIBROSIS; LUPUS ERYTHEMATOSUS NEPHRITIS; NONHUMAN; PROTEIN EXPRESSION; RENAL PROTECTION; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM;

ANIMALIA;

EID: 82155189416     PISSN: 15734080     EISSN: 18756662     Source Type: Journal    
DOI: 10.2174/157340810791233042     Document Type: Article

References (180)

1. Massague, J. The transforming growth factor-beta family. Annu. Rev. Cell. Biol., 1990, 6, 597-641.
2. Ando, T.; Okuda, S.; Tamaki, K.; Yoshitomi, K.; Fujishima, M. Localization of transforming growth factor-beta and latent transforming growth factor-beta binding protein in rat kidney. Kidney Int., 1995, 47, 733-739.
3. Qi, W.; Chen, X.; Poronnik, P.; Pollock, C.A. Transforming growth factor-beta/connective tissue growth factor axis in the kidney. Int. J. Biochem. Cell Biol., 2008, 40, 9-13.
4. MacKay, K.; Kondaiah, P.; Danielpour, D.; Austin, H.A., 3rd; Brown, P.D. Expression of transforming growth factor-beta 1 and beta 2 in rat glomeruli. Kidney Int., 1990, 38, 1095-1100.
5. Wilson, H.M.; Minto, A.W.; Brown, P.A.; Erwig, L.P.; Rees, A.J. Transforming growth factor-beta isoforms and glomerular injury in nephrotoxic nephritis. Kidney Int., 2000, 57, 2434-2444.
6. Annes, J.P.; Munger, J.S.; Rifkin, D.B. Making sense of latent TGFbeta activation. J. Cell. Sci., 2003, 116, 217-224.
7. Sato, Y.; Rifkin, D.B. Inhibition of endothelial cell movement by pericytes and smooth muscle cells: activation of a latent transforming growth factor-beta 1-like molecule by plasmin during coculture. J. Cell. Biol., 1989, 109, 309-315.
8. Yu, Q.; Stamenkovic, I. Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev., 2000, 14, 163-176.
9. Mu, D.; Cambier, S.; Fjellbirkeland, L.; Baron, J.L.; Munger, J.S.; Kawakatsu, H.; Sheppard, D.; Broaddus, V.C.; Nishimura, S.L. The integrin alpha(v)beta8 mediates epithelial homeostasis through MT1-MMP-dependent activation of TGF-beta1. J. Cell. Biol., 2002, 157, 493-507.
10. Munger, J.S.; Huang, X.; Kawakatsu, H.; Griffiths, M.J.; Dalton, S.L.; Wu, J.; Pittet, J.F.; Kaminski, N.; Garat, C.; Matthay, M.A.; Rifkin, D.B.; Sheppard, D. The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell, 1999, 96, 319-328.
11. Lyons, R.M.; Keski-Oja, J.; Moses, H.L. Proteolytic activation of latent transforming growth factor-beta from fibroblast-conditioned medium. J. Cell. Biol., 1988, 106, 1659-1665.
12. Murphy-Ullrich, J.E.; Poczatek, M. Activation of latent TGF-beta by thrombospondin-1: mechanisms and physiology. Cytokine Growth Factor Rev., 2000, 11, 59-69.
13. MacKay, K.; Striker, L.J.; Stauffer, J.W.; Doi, T.; Agodoa, L.Y.; Striker, G. E. Transforming growth factor-beta. Murine glomerular receptors and responses of isolated glomerular cells. J. Clin. Invest., 1989, 83, 1160-1167.
14. Shankland, S.J.; Pippin, J.; Pichler, R.H.; Gordon, K.L.; Friedman, S.; Gold, L.I.; Johnson, R.J.; Couser, W.G. Differential expression of transforming growth factor-beta isoforms and receptors in experimental membranous nephropathy. Kidney Int., 1996, 50, 116-124.
15. Derynck, R.; Zhang, Y.E. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature, 2003, 425, 577-584.
16. Blobe, G.C.; Schiemann, W.P.; Lodish, H.F. Role of transforming growth factor beta in human disease. N. Engl. J. Med., 2000, 342, 1350-1358.
17. Massague, J. Integration of Smad and MAPK pathways: a link and a linker revisited. Genes Dev., 2003, 17, 2993-2997.
18. Yakymovych, I.; Ten Dijke, P.; Heldin, C. H.; Souchelnytskyi, S. Regulation of Smad signaling by protein kinase C. FASEB J., 2001, 15, 553-555.
19. Masszi, A.; Di Ciano, C.; Sirokmany, G.; Arthur, W.T.; Rotstein, O.D.; Wang, J.; McCulloch, C.A.; Rosivall, L.; Mucsi, I.; Kapus, A. Central role for Rho in TGF-beta1-induced alpha-smooth muscle actin expression during epithelial-mesenchymal transition. Am. J. Physiol. Renal. Physiol., 2003, 284, F911-F924.
20. Muller, N.; Reinacher-Schick, A.; Baldus, S.; van Hengel, J.; Berx, G.; Baar, A.; van Roy, F.; Schmiegel, W.; Schwarte-Waldhoff, I. Smad4 induces the tumor suppressor E-cadherin and P-cadherin in colon carcinoma cells. Oncogene, 2002, 21, 6049-6058.
21. Feng, X.H.; Derynck, R. Specificity and versatility in tgf-beta signaling through Smads. Annu. Rev. Cell Dev. Biol., 2005, 21, 659-693.
22. Stemple, D.L. Vertebrate development: the fast track to nodal signalling. Curr. Biol., 2000, 10, R843-R846.
23. Schier, A.F. Nodal signaling in vertebrate development. Annu. Rev. Cell Dev. Biol., 2003, 19, 589-621.
24. Yamamoto, M.; Saijoh, Y.; Perea-Gomez, A.; Shawlot, W.; Behringer, R.R.; Ang, S.L.; Hamada, H.; Meno, C. Nodal antagonists regulate formation of the anteroposterior axis of the mouse embryo. Nature, 2004, 428, 387-392.
25. Zorn, A.M.; Wells, J.M. Molecular basis of vertebrate endoderm development. Int. Rev. Cytol., 2007, 259, 49-111.
26. ten Dijke, P.; Arthur, H.M. Extracellular control of TGFbeta signalling in vascular development and disease. Nat. Rev. Mol. Cell Biol., 2007, 8, 857-869.
27. Godin, R.E.; Takaesu, N.T.; Robertson, E.J.; Dudley, A.T. Regulation of BMP7 expression during kidney development. Development, 1998, 125, 3473-3482.
28. Cain, J.E.; Hartwig, S.; Bertram, J.F.; Rosenblum, N. D. Bone morphogenetic protein signaling in the developing kidney: present and future. Differentiation, 2008, 76, 831-842.
29. Godin, R.E.; Robertson, E.J.; Dudley, A.T. Role of BMP family members during kidney development. Int. J. Dev. Biol. 1999, 43, 405-411.
30. Dudley, A.T.; Lyons, K.M.; Robertson, E.J. A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye. Genes Dev., 1995, 9, 2795-2807.
31. Dudley, A.T.; Robertson, E.J. Overlapping expression domains of bone morphogenetic protein family members potentially account for limited tissue defects in BMP7 deficient embryos. Dev. Dyn. 1997, 208, 349-362.
32. Hartwig, S.; Hu, M.C.; Cella, C.; Piscione, T.; Filmus, J.; Rosenblum, N.D. Glypican-3 modulates inhibitory Bmp2-Smad signaling to control renal development in vivo. Mech. Dev., 2005, 122, 928-938.
33. Miyazaki, Y.; Oshima, K.; Fogo, A.; Hogan, B.L.; Ichikawa, I. Bone morphogenetic protein 4 regulates the budding site and elongation of the mouse ureter. J. Clin. Invest., 2000, 105, 863-873.
34. Miyazaki, Y.; Oshima, K.; Fogo, A.; Ichikawa, I. Evidence that bone morphogenetic protein 4 has multiple biological functions during kidney and urinary tract development. Kidney Int., 2003, 63, 835-844.
35. Dockrell, M.E.; Phanish, M.K.; Hendry, B.M. Tgf-beta autoinduction and connective tissue growth factor expression in human renal tubule epithelial cells requires N-ras. Nephron Exp. Nephrol., 2009, 112, e71-e79.
36. Lane, A.; Johnson, D.W.; Pat, B.; Winterford, C.; Endre, Z.; Wei, M.; Gobe, G. C. Interacting roles of myofibroblasts, apoptosis and fibrogenic growth factors in the pathogenesis of renal tubulointerstitial fibrosis. Growth Factors, 2002, 20, 109-119.
37. Miyajima, A.; Chen, J.; Lawrence, C.; Ledbetter, S.; Soslow, R.A.; Stern, J.; Jha, S.; Pigato, J.; Lemer, M.L.; Poppas, D.P.; Vaughan, E.D.; Felsen, D. Antibody to transforming growth factor-beta ameliorates tubular apoptosis in unilateral ureteral obstruction. Kidney Int., 2000, 58, 2301-2313.
38. Docherty, N.G.; O'Sullivan, O.E.; Healy, D.A.; Murphy, M.; O'Neill, A.J.; Fitzpatrick, J.M.; Watson, R.W. TGF-beta1-induced EMT can occur independently of its proapoptotic effects and isaided by EGF receptor activation. Am. J. Physiol. Renal Physiol., 2006, 290, F1202-F1212.
39. Schiffer, M.; Bitzer, M.; Roberts, I.S.; Kopp, J.B.; ten Dijke, P.; Mundel, P.; Bottinger, E.P. Apoptosis in podocytes induced by TGF-beta and Smad7. J. Clin. Invest., 2001, 108, 807-816.
40. Moses, H.L.; Arteaga, C.L.; Alexandrow, M.G.; Dagnino, L.; Kawabata, M.; Pierce, D.F., Jr.; Serra, R. TGF beta regulation of cell proliferation. Princess Takamatsu Symp., 1994, 24, 250-263.
41. Liu, Y., Renal fibrosis: new insights into the pathogenesis and therapeutics. Kidney Int., 2006, 69, 213-217.
42. Kaneto, H.; Morrissey, J.; Klahr, S. Increased expression of TGFbeta 1 mRNA in the obstructed kidney of rats with unilateral ureteral ligation. Kidney Int., 1993, 44, 313-321.
43. Bautista-Garcia, P.; Sanchez-Lozada, L.G.; Cristobal-Garcia, M.; Tapia, E.; Soto, V.; Avila-Casado, M.C.; Marquez-Velasco, R.; Bojalil, R.; Franco, M.; Herrera-Acosta, J. Chronic inhibition of NOS-2 ameliorates renal injury, as well as COX-2 and TGF-beta 1 overexpression in 5/6 nephrectomized rats. Nephrol. Dial. Transplant., 2006, 21, 3074-3081.
44. Sharma, K.; Ziyadeh, F. N. Renal hypertrophy is associated with upregulation of TGF-beta 1 gene expression in diabetic BB rat and NOD mouse. Am. J. Physiol., 1994, 267, F1094-F1101.
45. Kasuga, H.; Ito, Y.; Sakamoto, S.; Kawachi, H.; Shimizu, F.; Yuzawa, Y.; Matsuo, S. Effects of anti-TGF-beta type II receptor antibody on experimental glomerulonephritis. Kidney Int., 2001, 60, 1745-1755.
46. Ma, L.J.; Jha, S.; Ling, H.; Pozzi, A.; Ledbetter, S.; Fogo, A.B. Divergent effects of low versus high dose anti-TGF-beta antibody in puromycin aminonucleoside nephropathy in rats. Kidney Int., 2004, 65, 106-115.
47. Sharma, K.; Jin, Y.; Guo, J.; Ziyadeh, F.N. Neutralization of TGFbeta 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.
48. Ma, L.J.; Nakamura, S.; Aldigier, J.C.; Rossini, M.; Yang, H.; Liang, X.; Nakamura, I.; Marcantoni, C.; Fogo, A.B. Regression of glomerulosclerosis with high-dose angiotensin inhibition is linked to decreased plasminogen activator inhibitor-1. J. Am. Soc. Nephrol., 2005, 16, 966-976.
49. Brown, N.J.; Nakamura, S.; Ma, L.; Nakamura, I.; Donnert, E.; Freeman, M.; Vaughan, D.E.; Fogo, A.B. Aldosterone modulates plasminogen activator inhibitor-1 and glomerulosclerosis in vivo. Kidney Int., 2000, 58, 1219-1227.
50. Pohlers, D.; Brenmoehl, J.; Loffler, I.; Muller, C. K.; Leipner, C.; Schultze-Mosgau, S.; Stallmach, A.; Kinne, R.W.; Wolf, G. TGFbeta and fibrosis in different organs-molecular pathway imprints. Biochim Biophys. Acta., 2009, 1792, 746-756.
51. Allen, J.B.; Manthey, C.L.; Hand, A.R.; Ohura, K.; Ellingsworth, L.; Wahl, S.M. Rapid onset synovial inflammation and hyperplasia induced by transforming growth factor beta. J. Exp. Med., 1990, 171, 231-247.
52. Brandes, M.E.; Allen, J.B.; Ogawa, Y.; Wahl, S.M. Transforming growth factor beta 1 suppresses acute and chronic arthritis in experimental animals. J. Clin. Invest., 1991, 87, 1108-1113.
53. Taylor, A.W. Review of the activation of TGF-beta in immunity. J. Leukoc. Biol., 2009, 85, 29-33.
54. Kulkarni, A.B.; Huh, C.G.; Becker, D.; Geiser, A.; Lyght, M.; Flanders, K.C.; Roberts, A.B.; Sporn, M.B.; Ward, J.M.; Karlsson, S. Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc. Natl. Acad. Sci. U.S.A., 1993, 90, 770-774.
55. Kulkarni, A.B.; Karlsson, S. Transforming growth factor-beta 1 knockout mice. A mutation in one cytokine gene causes a dramatic inflammatory disease. Am. J. Pathol., 1993, 143, 3-9.
56. Christ, M.; McCartney-Francis, N.L.; Kulkarni, A.B.; Ward, J.M.; Mizel, D.E.; Mackall, C.L.; Gress, R.E.; Hines, K.L.; Tian, H.; Karlsson, S. Immune dysregulation in TGF-beta 1-deficient mice. J. Immunol., 1994, 153, 1936-1946.
57. Bottinger, E.P.; Letterio, J.J.; Roberts, A.B. Biology of TGF-beta in knockout and transgenic mouse models. Kidney Int., 1997, 51, 1355-1360.
58. Glinka, Y.; Prud'homme, G.J. Neuropilin-1 is a receptor for transforming growth factor beta-1, activates its latent form, and promotes regulatory T cell activity. J. Leukoc. Biol., 2008, 84, 302-310.
59. Sakaguchi, S. Regulatory T cells: key controllers of immunologic self-tolerance. Cell, 2000, 101, 455-458.
60. Bommireddy, R.; Doetschman, T. TGFbeta1 and Treg cells: alliance for tolerance. Trends Mol. Med., 2007, 13, 492-501.
61. Nakamura, K.; Kitani, A.; Fuss, I.; Pedersen, A.; Harada, N.; Nawata, H.; Strober, W. TGF-beta 1 plays an important role in the mechanism of CD4+CD25+ regulatory T cell activity in both humans and mice. J. Immunol., 2004, 172, 834-842.
62. Luo, X.; Tarbell, K.V.; Yang, H.; Pothoven, K.; Bailey, S.L.; Ding, R.; Steinman, R.M.; Suthanthiran, M. Dendritic cells with TGFbeta1 differentiate naive CD4+CD25-T cells into islet-protective Foxp3+ regulatory T cells. Proc. Natl. Acad. Sci. U.S.A., 2007, 104, 2821-2826.
63. Marie, J.C.; Liggitt, D.; Rudensky, A.Y. Cellular mechanisms of fatal early-onset autoimmunity in mice with the T cell-specific targeting of transforming growth factor-beta receptor. Immunity, 2006, 25, 441-454.
64. Li, M.O.; Sanjabi, S.; Flavell, R.A. Transforming growth factorbeta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and-independent mechanisms. Immunity, 2006, 25, 455-471.
65. Petrausch, U.; Jensen, S.M.; Twitty, C.; Poehlein, C.H.; Haley, D.P.; Walker, E.B.; Fox, B.A. Disruption of TGF-{beta} signaling prevents the generation of tumor-sensitized regulatory T cells and facilitates therapeutic antitumor immunity. J. Immunol., 2009, 183, 3682-3689, Epub 2009 Aug 19.
66. Robertson, H.; Kirby, J. A., Post-transplant renal tubulitis: the recruitment, differentiation and persistence of intra-epithelial T cells. Am. J. Transplant., 2003, 3, 3-10.
67. Hewitt, C.W.; Strande, L.; Santos, M.; Goodman, M.; Tarnoff, M.; Zaontz, M.R.; DelRossi, A.J.; Doolin, E.J. Rat renal allograft tolerance is associated with local TGF-beta and absence of IL-2r expression within chimeric immunocytic foci. Transplant. Proc., 1997, 29, 2183-2184.
68. Wang, S.; Jiang, J.; Guan, Q.; Lan, Z.; Wang, H.; Nguan, C.Y.; Jevnikar, A.M.; Du, C. Reduction of Foxp3-expressing regulatory T cell infiltrates during the progression of renal allograft rejection in a mouse model. Transpl. Immunol., 2008, 19, 93-102.
69. Citterio, F.; Pozzetto, U.; Romagnoli, J.; Tondolo, E.; Silvestri, P.; Nanni, G.; Castagneto, M., Plasma levels of transforming growth factor-beta1 in renal transplant recipients receiving different immunosuppressive regimens. Transplant. Proc., 2004, 36 (3), 698-9.
70. Hoffmann, S.; Park, J.; Jacobson, L.M.; Muehrer, R.J.; Lorentzen, D.; Kleiner, D.; Becker, Y.T.; Hullett, D.A.; Mannon, R.; Kirk, A.D.; Becker, B.N. Donor genomics influence graft events: the effect of donor polymorphisms on acute rejection and chronic allograft nephropathy. Kidney Int., 2004, 66, 1686-1693.
71. Border, W.A.; Noble, N.A. Interactions of transforming growth factor-beta and angiotensin II in renal fibrosis. Hypertension, 1998, 31, 181-188.
72. Gaedeke, J.; Peters, H.; Noble, N.A.; Border, W.A. Angiotensin II, TGF-beta and renal fibrosis. Contrib. Nephrol., 2001, 135, 153-160.
73. Wolf, G.; Mueller, E.; Stahl, R.A.; Ziyadeh, F.N. Angiotensin IIinduced hypertrophy of cultured murine proximal tubular cells is mediated by endogenous transforming growth factor-beta. J. Clin. Invest., 1993, 92, 1366-1372.
74. Wolf, G.; Neilson, E.G. Angiotensin II as a hypertrophogenic cytokine for proximal tubular cells. Kidney Int. Suppl., 1993, 39, S100-S107.
75. Kagami, S.; Border, W.A.; Miller, D.E.; Noble, N.A. Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-beta expression in rat glomerular mesangial cells. J. Clin. Invest., 1994, 93, 2431-2437.
76. Vieitez, P.; Gomez, O.; Uceda, E.R.; Vera, M.E.; Molina-Holgado, E. Systemic and local effects of angiotensin II blockade in experimental diabetic nephropathy. J. Renin Angiotensin Aldosterone Syst., 2008, 9, 96-102.
77. Zhang, Z.; Zhang, Y.; Ning, G.; Deb, D.K.; Kong, J.; Li, Y.C. Combination therapy with AT1 blocker and vitamin D analog markedly ameliorates diabetic nephropathy: blockade of compensatory renin increase. Proc. Natl. Acad. Sci. USA, 2008, 105, 15896-15901.
78. Agarwal, R.; Siva, S.; Dunn, S.R.; Sharma, K. Add-on angiotensin II receptor blockade lowers urinary transforming growth factorbeta levels. Am. J. Kidney Dis., 2002, 39, 486-492.
79. Song, J.H.; Cha, S.H.; Lee, H.J.; Lee, S.W.; Park, G.H.; Lee, S.W.; Kim, M.J. Effect of low-dose dual blockade of renin-angiotensin system on urinary TGF-beta in type 2 diabetic patients with advanced kidney disease. Nephrol. Dial. Transplant., 2006, 21, 683-689.
80. Honkanen, E.; Teppo, A.M.; Tornroth, T.; Groop, P.H.; Gronhagen-Riska, C. Urinary transforming growth factor-beta 1 in membranous glomerulonephritis. Nephrol. Dial. Transplant., 1997, 12, 2562-2568.
81. Park, H.C.; Xu, Z.G.; Choi, S.; Goo, Y.S.; Kang, S.W.; Choi, K.H.; Ha, S.K.; Lee, H.Y.; Han, D.S. Effect of losartan and amlodipine on proteinuria and transforming growth factor-beta1 in patients with IgA nephropathy. Nephrol. Dial. Transplant., 2003, 18, 1115-1121.
82. Loskutoff, D.J.; Edgington, T.S. An inhibitor of plasminogen activator in rabbit endothelial cells. J. Biol. Chem., 1981, 256, 4142-4145.
83. H.R. Pleiotropic functions of plasminogen activator inhibitor-1. J. Thromb. Haemost., 2005, 3, 35-45.
84. Ma, L.J.; Fogo, A.B. PAI-1 and kidney fibrosis. Front. Biosci., 2009, 14, 2028-2041.
85. Fogo, A.B. Renal fibrosis: not just PAI-1 in the sky. J. Clin. Invest., 2003, 112, 326-328.
86. Ma, L.J.; Fogo, A.B. Angiotensin as inducer of plasminogen activator inhibitor-1 and fibrosis. Contrib. Nephrol., 2001, 135, 161-170.
87. Fogo, A.B. Renal fibrosis and the renin-angiotensin system. Adv. Nephrol. Necker. Hosp., 2001, 31, 69-87.
88. A.B. The role of angiotensin II and plasminogen activator inhibitor-1 in progressive glomerulosclerosis. Am. J. Kidney. Dis., 2000, 35, 179-188.
89. Nakamura, S.; Nakamura, I.; Ma, L.; Vaughan, D.E.; Fogo, A.B. Plasminogen activator inhibitor-1 expression is regulated by the angiotensin type 1 receptor in vivo. Kidney Int., 2000, 58, 251-259.
90. Eddy, A.A.; Fogo, A.B. Plasminogen activator inhibitor-1 in chronic kidney disease: evidence and mechanisms of action. J. Am. Soc. Nephrol., 2006, 17, 2999-3012.
91. Wilson, H.M.; Reid, F.J.; MacLeod, A.M.; Haites, N.E.; Booth, N.A. Transforming growth factor beta (TGF-beta) regulates the matrix-associated plasminogen activator inhibitor 1 (PAI-1) in glomerular mesangial and epithelial cells. Exp. Nephrol., 1995, 3, 141-142.
92. Motojima, M.; Kakuchi, J.; Yoshioka, T. Association of TGF-beta signaling in angiotensin II-induced PAI-1 mRNA upregulation in mesangial cells: role of PKC. Biochim. Biophys. Acta., 1999, 1449, 217-226.
93. Vayalil, P.K.; Iles, K.E.; Choi, J.; Yi, A.K.; Postlethwait, E.M.; Liu, R.M. Glutathione suppresses TGF-beta-induced PAI-1 expression by inhibiting p38 and JNK MAPK and the binding of AP-1, SP-1, and Smad to the PAI-1 promoter. Am. J. Physiol. Lung Cell. Mol. Physiol., 2007, 293, L1281-L1292.
94. Guo, B.; Inoki, K.; Isono, M.; Mori, H.; Kanasaki, K.; Sugimoto, T.; Akiba, S.; Sato, T.; Yang, B.; Kikkawa, R.; Kashiwagi, A.; Haneda, M.; Koya, D. MAPK/AP-1-dependent regulation of PAI-1 gene expression by TGF-beta in rat mesangial cells. Kidney Int., 2005, 68, 972-984.
95. Dong, C.; Zhu, S.; Wang, T.; Yoon, W.; Goldschmidt-Clermont, P.J. Upregulation of PAI-1 is mediated through TGF-beta/Smad pathway in transplant arteriopathy. J. Heart Lung Transplant., 2002, 21, 999-1008.
96. Vaughan, D.E. PAI-1 and TGF-beta: unmasking the real driver of TGF-beta-induced vascular pathology. Arterioscler. Thromb. Vasc. Biol., 2006, 26, 679-680.
97. Krag, S.; Danielsen, C.C.; Carmeliet, P.; Nyengaard, J.; Wogensen, L. Plasminogen activator inhibitor-1 gene deficiency attenuates TGF-beta1-induced kidney disease. Kidney Int., 2005, 68, 2651-2666.
98. Chen, X.M.; Qi, W.; Pollock, C.A. CTGF and chronic kidney fibrosis. Front. Biosci. (Schol Ed.), 2009, 1, 132-141.
99. Wahab, N.; Cox, D.; Witherden, A.; Mason, R.M. Connective tissue growth factor (CTGF) promotes activated mesangial cell survival via up-regulation of mitogen-activated protein kinase phosphatase-1 (MKP-1). Biochem. J., 2007, 406, 131-138.
100. Tu, Z.; Shi, Y.; Wang, J.; Bao, J.; Bu, H. Upregulation of connective tissue growth factor in a rat model of chronic allograft nephropathy. Nephrology (Carlton), 2007, 12, 166-171.
101. Cheng, O.; Thuillier, R.; Sampson, E.; Schultz, G.; Ruiz, P.; Zhang, X.; Yuen, P.S.; Mannon, R.B. Connective tissue growth factor is a biomarker and mediator of kidney allograft fibrosis. Am. J. Transplant., 2006, 6, 2292-2306.
102. Wahab, N.A.; Weston, B.S.; Mason, R.M. Modulation of the TGFbeta/Smad signaling pathway in mesangial cells by CTGF/CCN2. Exp. Cell Res., 2005, 307, 305-314.
103. Wahab, N.A.; Schaefer, L.; Weston, B.S.; Yiannikouris, O.; Wright, A.; Babelova, A.; Schaefer, R.; Mason, R.M. Glomerular expression of thrombospondin-1, transforming growth factor beta and connective tissue growth factor at different stages of diabetic nephropathy and their interdependent roles in mesangial response to diabetic stimuli. Diabetologia, 2005, 48, 2650-2660.
104. Qi, W.; Twigg, S.; Chen, X.; Polhill, T.S.; Poronnik, P.; Gilbert, R.E.; Pollock, C.A. Integrated actions of transforming growth factor-beta1 and connective tissue growth factor in renal fibrosis. Am. J. Physiol. Renal Physiol., 2005, 288, F800-F809.
105. Yokoi, H.; Sugawara, A.; Mukoyama, M.; Mori, K.; Makino, H.; Suganami, T.; Nagae, T.; Yahata, K.; Fujinaga, Y.; Tanaka, I.; Nakao, K. Role of connective tissue growth factor in profibrotic action of transforming growth factor-beta: a potential target for preventing renal fibrosis. Am. J. Kidney Dis., 2001, 38, S134-S138.
106. Annes, J.P.; Chen, Y.; Munger, J.S.; Rifkin, D.B. Integrin alphaVbeta6-mediated activation of latent TGF-beta requires the latent TGF-beta binding protein-1. J. Cell Biol., 2004, 165, 723-734.
107. Yang, Z.; Mu, Z.; Dabovic, B.; Jurukovski, V.; Yu, D.; Sung, J.; Xiong, X.; Munger, J.S. Absence of integrin-mediated TGFbeta1 activation in vivo recapitulates the phenotype of TGFbeta1-null mice. J. Cell Biol., 2007, 176, 787-793.
108. Kaplan, D.H.; Li, M.O.; Jenison, M.C.; Shlomchik, W.D.; Flavell, R.A.; Shlomchik, M.J. Autocrine/paracrine TGFbeta1 is required for the development of epidermal Langerhans cells. J. Exp. Med., 2007, 204, 2545-2552.
109. Ma, L.J.; Yang, H.; Gaspert, A.; Carlesso, G.; Barty, M.M.; Davidson, J.M.; Sheppard, D.; Fogo, A.B. Transforming growth factorbeta-dependent and-independent pathways of induction of tubulointerstitial fibrosis in beta6(-/-) mice. Am. J. Pathol., 2003, 163, 1261-1273.
110. Sosne, G.; Siddiqi, A.; Kurpakus-Wheater, M. Thymosin-beta4 inhibits corneal epithelial cell apoptosis after ethanol exposure in vitro. Invest. Ophthalmol. Vis. Sci., 2004, 45, 1095-1100.
111. Bock-Marquette, I.; Saxena, A.; White, M.D.; Dimaio, J.M.; Srivastava, D. Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature, 2004, 432, 466-472.
112. Smart, N.; Risebro, C.A.; Melville, A.A.; Moses, K.; Schwartz, R.J.; Chien, K.R.; Riley, P.R. Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization. Nature, 2007, 445, 177-182.
113. Malinda, K.M.; Sidhu, G.S.; Mani, H.; Banaudha, K.; Maheshwari, R.K.; Goldstein, A.L.; Kleinman, H.K. Thymosin beta4 accelerates wound healing. J. Invest. Dermatol., 1999, 113, 364-368.
114. Sosne, G.; Xu, L.; Prach, L.; Mrock, L.K.; Kleinman, H.K.; Letterio, J.J.; Hazlett, L.D.; Kurpakus-Wheater, M. Thymosin beta 4 stimulates laminin-5 production independent of TGF-beta. Exp. Cell Res., 2004, 293, 175-183.
115. Xu, B.J.; Shyr, Y.; Liang, X.; Ma, L.J.; Donnert, E.M.; Roberts, J.D.; Zhang, X.; Kon, V.; Brown, N.J.; Caprioli, R.M.; Fogo, A.B. Proteomic patterns and prediction of glomerulosclerosis and its mechanisms. J. Am. Soc. Nephrol., 2005, 16, 2967-2975.
116. Cavasin, M. A.; Rhaleb, N. E.; Yang, X. P.; Carretero, O. A. Prolyl oligopeptidase is involved in release of the antifibrotic peptide Ac-SDKP. Hypertension, 2004, 43, 1140-1145.
117. Peng, H.; Carretero, O.A.; Raij, L.; Yang, F.; Kapke, A.; Rhaleb, N.E. Antifibrotic effects of N-acetyl-seryl-aspartyl-Lysyl-proline on the heart and kidney in aldosterone-salt hypertensive rats. Hypertension 2001, 37 (2 Part 2), 794-800.
118. Rhaleb, N.E.; Peng, H.; Harding, P.; Tayeh, M.; LaPointe, M.C.; Carretero, O.A. Effect of N-acetyl-seryl-aspartyl-lysyl-proline on DNA and collagen synthesis in rat cardiac fibroblasts. Hypertension, 2001, 37, 827-832.
119. Rhaleb, N.E.; Peng, H.; Yang, X. P.; Liu, Y.H.; Mehta, D.; Ezan, E.; Carretero, O.A. Long-term effect of N-acetyl-seryl-aspartyllysyl-proline on left ventricular collagen deposition in rats with 2-kidney, 1-clip hypertension. Circulation, 2001, 103, 3136-3141.
120. Peng, H.; Carretero, O.A.; Brigstock, D.R.; Oja-Tebbe, N.; Rhaleb, N.E. Ac-SDKP reverses cardiac fibrosis in rats with renovascular hypertension. Hypertension, 2003, 42, 1164-1170.
121. Peng, H.; Carretero, O.A.; Vuljaj, N.; Liao, T.D.; Motivala, A.; Peterson, E.L.; Rhaleb, N.E. Angiotensin-converting enzyme inhibitors: a new mechanism of action. Circulation, 2005, 112, 2436-2445.
122. Rasoul, S.; Carretero, O.A.; Peng, H.; Cavasin, M.A.; Zhuo, J.; Sanchez-Mendoza, A.; Brigstock, D.R.; Rhaleb, N.E. Antifibrotic effect of Ac-SDKP and angiotensin-converting enzyme inhibition in hypertension. J. Hypertens., 2004, 22, 593-603.
123. Kanasaki, K.; Koya, D.; Sugimoto, T.; Isono, M.; Kashiwagi, A.; Haneda, M. N-Acetyl-seryl-aspartyl-lysyl-proline inhibits TGFbeta-mediated plasminogen activator inhibitor-1 expression via inhibition of Smad pathway in human mesangial cells. J. Am. Soc. Nephrol., 2003, 14, 863-872.
124. Morris-Stiff, G. TGFbeta-1 and the development of chronic graft nephropathy: relative roles of gene, mRNA and protein. Ann. R. Coll. Surg. Engl., 2005, 87, 326-330.
125. Hutchinson, I. V.; Pravica, V.; Perrey, C.; Sinnott, P. Cytokine gene polymorphisms and relevance to forms of rejection. Transplant. Proc., 1999, 31, 734-736.
126. Ochsner, S.; Guo, Z.; Binswanger, U.; Knoflach, A. TGF-beta 1 gene expression in stable renal transplant recipients: influence of TGF-beta 1 gene polymorphism and immunosuppression. Transplant. Proc., 2002, 34, 2901-2903.
127. Cambien, F.; Ricard, S.; Troesch, A.; Mallet, C.; Generenaz, L.; Evans, A.; Arveiler, D.; Luc, G.; Ruidavets, J.B.; Poirier, O. Polymorphisms of the transforming growth factor-beta 1 gene in relation to myocardial infarction and blood pressure. The Etude Cas-Temoin de l'Infarctus du Myocarde (ECTIM) Study. Hypertension, 1996, 28, 881-887.
128. Cho, J.H.; Huh, S.; Kwon, T.G.; Choi, J.Y.; Hur, I.K.; Lee, E.Y.; Park, S.H.; Kim, Y.L.; Kim, C.D. Association of C-509T and T869C polymorphisms of transforming growth factor-beta1 gene with chronic allograft nephropathy and graft survival in Korean renal transplant recipients. Transplant. Proc., 2008, 40, 2355-2360.
129. Freedman, B.I.; Yu, H.; Spray, B.J.; Rich, S.S.; Rothschild, C.B.; Bowden, D.W. Genetic linkage analysis of growth factor loci and end-stage renal disease in African Americans. Kidney Int., 1997, 51, 819-825.
130. Suthanthiran, M.; Gerber, L.M.; Schwartz, J.E.; Sharma, V.K.; Medeiros, M.; Marion, R.; Pickering, T.G.; August, P. Circulating transforming growth factor-beta1 levels and the risk for kidney disease in African Americans. Kidney Int., 2009, 76, 72-80.
131. Pfeiffer, A.; Middelberg-Bisping, K.; Drewes, C.; Schatz, H. Elevated plasma levels of transforming growth factor-beta 1 in NIDDM. Diabetes Care, 1996, 19, 1113-1117.
132. Campistol, J.M.; Inigo, P.; Jimenez, W.; Lario, S.; Clesca, P.H.; Oppenheimer, F.; Rivera, F. Losartan decreases plasma levels of TGF-beta1 in transplant patients with chronic allograft nephropathy. Kidney Int., 1999, 56, 714-719.
133. Inigo, P.; Campistol, J.M.; Lario, S.; Piera, C.; Campos, B.; Bescos, M.; Oppenheimer, F.; Rivera, F. Effects of losartan and amlodipine on intrarenal hemodynamics and TGF-beta(1) plasma levels in a crossover trial in renal transplant recipients. J. Am. Soc. Nephrol., 2001, 12, 822-827.
134. Kim, J.H.; Kim, B.K.; Moon, K.C.; Hong, H.K.; Lee, H.S. Activation of the TGF-beta/Smad signaling pathway in focal segmental glomerulosclerosis. Kidney Int., 2003, 64, 1715-1721.
135. Chan, R.W.; Lai, F.M.; Li, E.K.; Tam, L.S.; Wong, T.Y.; Szeto, C.Y.; Li, P.K.; Szeto, C.C. Expression of chemokine and fibrosing factor messenger RNA in the urinary sediment of patients with lupus nephritis. Arthritis Rheum., 2004, 50, 2882-2890.
136. Yamamoto, T.; Noble, N.A.; Cohen, A.H.; Nast, C.C.; Hishida, A.; Gold, L.I.; Border, W.A. Expression of transforming growth factorbeta isoforms in human glomerular diseases. Kidney Int., 1996, 49, 461-469.
137. Yoshioka, K.; Takemura, T.; Murakami, K.; Okada, M.; Hino, S.; Miyamoto, H.; Maki, S. Transforming growth factor-beta protein and mRNA in glomeruli in normal and diseased human kidneys. Lab. Invest. 1993, 68, 154-163.
138. Goumenos, D.S.; Tsakas, S.; El Nahas, A.M.; Alexandri, S.; Oldroyd, S.; Kalliakmani, P.; Vlachojannis, J.G. Transforming growth factor-beta(1) in the kidney and urine of patients with glomerular disease and proteinuria. Nephrol. Dial. Transplant., 2002, 17, 2145-2152.
139. Teppo, A.M.; Honkanen, E.; Finne, P.; Tornroth, T.; Gronhagen-Riska, C. Increased urinary excretion of alpha1-microglobulin at 6 months after transplantation is associated with urinary excretion of transforming growth factor-beta1 and indicates poor long-term renal outcome. Transplantation 2004, 78, 719-724.
140. M. Urine excretion of transforming growth factorbeta1 in chronic allograft nephropathy. Ann. Transplant., 1999, 4, 23-28.
141. Grandaliano, G.; Di Paolo, S.; Monno, R.; Stallone, G.; Ranieri, E.; Pontrelli, P.; Gesualdo, L.; Schena, F.P. Protease-activated receptor 1 and plasminogen activator inhibitor 1 expression in chronic allograft nephropathy: the role of coagulation and fibrinolysis in renal graft fibrosis. Transplantation, 2001, 72, 1437-1443.
142. De Muro, P.; Faedda, R.; Fresu, P.; Masala, A.; Cigni, A.; Concas, G.; Mela, M.G.; Satta, A.; Carcassi, A.; Sanna, G.M.; Cherchi, G.M. Urinary transforming growth factor-beta 1 in various types of nephropathy. Pharmacol. Res., 2004, 49, 293-298.
143. Murakami, K.; Takemura, T.; Hino, S.; Yoshioka, K. Urinary transforming growth factor-beta in patients with glomerular diseases. Pediatr. Nephrol., 1997, 11, 334-336.
144. Cha, D.R.; Kim, I.S.; Kang, Y.S.; Han, S.Y.; Han, K.H.; Shin, C.; Ji, Y.H.; Kim, N.H. Urinary concentration of transforming growth factor-beta-inducible gene-h3(beta ig-h3) in patients with Type 2 diabetes mellitus. Diabet. Med., 2005, 22, 14-20.
145. Song, J.H.; Lee, S.W.; Suh, J.H.; Kim, E.S.; Hong, S.B.; Kim, K.A.; Kim, M.J. The effects of dual blockade of the reninangiotensin system on urinary protein and transforming growth factor-beta excretion in 2 groups of patients with IgA and diabetic nephropathy. Clin. Nephrol., 2003, 60, 318-326.
146. Praga, M.; Andrade, C.F.; Luno, J.; Arias, M.; Poveda, R.; Mora, J.; Prat, M.V.; Rivera, F.; Galceran, J.M.; Ara, J.M.; Aguirre, R.; Bernis, C.; Marin, R.; Campistol, J.M. Antiproteinuric efficacy of losartan in comparison with amlodipine in non-diabetic proteinuric renal diseases: a double-blind, randomized clinical trial. Nephrol. Dial. Transplant., 2003, 18, 1806-1813.
147. Mifsud, S.; Kelly, D.J.; Qi, W.; Zhang, Y.; Pollock, C.A.; Wilkinson-Berka, J.L.; Gilbert, R.E. Intervention with tranilast attenuates renal pathology and albuminuria in advanced experimental diabetic nephropathy. Nephron. Physiol., 2003, 95, 83-91.
148. Lasky, J. Pirfenidone. Drugs, 2004, 7, 166-172.
149. Heeg, M.H.; Koziolek, M.J.; Vasko, R.; Schaefer, L.; Sharma, K.; Muller, G.A.; Strutz, F. The antifibrotic effects of relaxin in human renal fibroblasts are mediated in part by inhibition of the Smad2 pathway. Kidney Int., 2005, 68, 96-109.
150. Yu, L.; Border, W.A.; Anderson, I.; McCourt, M.; Huang, Y.; Noble, N.A. Combining TGF-beta inhibition and angiotensin II blockade results in enhanced antifibrotic effect. Kidney Int., 2004, 66, 1774-1784.
151. Benigni, A.; Zoja, C.; Corna, D.; Zatelli, C.; Conti, S.; Campana, M.; Gagliardini, E.; Rottoli, D.; Zanchi, C.; Abbate, M.; Ledbetter, S.; Remuzzi, G. Add-on anti-TGF-beta antibody to ACE inhibitor arrests progressive diabetic nephropathy in the rat. J. Am. Soc. Nephrol., 2003, 14, 1816-1824.
152. Yang, H.C.; Ma, L.J.; Ma, J.; Fogo, A.B. Peroxisome proliferatoractivated receptor-gamma agonist is protective in podocyte injuryassociated sclerosis. Kidney Int., 2006, 69, 1756-1764.
153. Qin, J.; Zhang, Z.; Liu, J.; Sun, L.; Hu, L.; Cooper, M.E.; Cao, Z. Effects of the combination of an angiotensin II antagonist with an HMG-CoA reductase inhibitor in experimental diabetes. Kidney Int., 2003, 64, 565-571.
154. Juknevicius, I.; Segal, Y.; Kren, S.; Lee, R.; Hostetter, T.H. Effect of aldosterone on renal transforming growth factor-beta. Am. J. Physiol. Renal Physiol., 2004, 286, F1059-F1062.
155. Ziyadeh, F.N.; Hoffman, B.B.; Han, D.C.; Iglesias-de La Cruz, M.C.; Hong, S.W.; Isono, M.; Chen, S.; McGowan, T.A.; Sharma, K. Long-term prevention of renal insufficiency, excess matrix gene expression, and glomerular mesangial matrix expansion by treatment with monoclonal antitransforming growth factor-beta antibody in db/db diabetic mice. Proc. Natl. Acad. Sci. USA, 2000, 97, 8015-8020.
156. Chen, S.; Iglesias-de La Cruz, M.C.; Jim, B.; Hong, S.W.; Isono, M.; Ziyadeh, F.N. Reversibility of established diabetic glomerulopathy by anti-TGF-beta antibodies in db/db mice. Biochem. Biophys. Res. Commun., 2003, 300, 16-22.
157. Brosius, F.C. 3rd. New insights into the mechanisms of fibrosis and sclerosis in diabetic nephropathy. Rev. Endocr. Metab. Disord., 2008, 9, 245-254.
158. El Chaar, M.; Chen, J.; Seshan, S. V.; Jha, S.; Richardson, I.; Ledbetter, S.R. Vaughan, E.D., Jr.; Poppas, D.P.; Felsen, D. Effect of combination therapy with enalapril and the TGF-beta antagonist 1D11 in unilateral ureteral obstruction. Am. J. Physiol. Renal Physiol., 2007, 292, F1291-F1301.
159. Denton, C.P.; Merkel, P.A.; Furst, D.E.; Khanna, D.; Emery, P.; Hsu, V.M.; Silliman, N.; Streisand, J.; Powell, J.; Akesson, A.; Coppock, J.; Hoogen, F.; Herrick, A.; Mayes, M.D.; Veale, D.; Haas, J.; Ledbetter, S.; Korn, J.H.; Black, C.M.; Seibold, J.R. Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebocontrolled phase I/II trial of CAT-192. Arthritis Rheum., 2007, 56, 323-333.
160. Khaw, P.; Grehn, F.; Hollo, G.; Overton, B.; Wilson, R.; Vogel, R.; Smith, Z. A phase III study of subconjunctival human antitransforming growth factor beta(2) monoclonal antibody (CAT-152) to prevent scarring after first-time trabeculectomy. Ophthalmology, 2007, 114, 1822-1830.
161. Han, D.C.; Hoffman, B.B.; Hong, S.W.; Guo, J.; Ziyadeh, F.N. Therapy with antisense TGF-beta1 oligodeoxynucleotides reduces kidney weight and matrix mRNAs in diabetic mice. Am. J. Physiol. Renal Physiol., 2000, 278, F628-F634.
162. Nemunaitis, J.; Dillman, R.O.; Schwarzenberger, P.O.; Senzer, N.; Cunningham, C.; Cutler, J.; Tong, A.; Kumar, P.; Pappen, B.; Hamilton, C.; DeVol, E.; Maples, P.B.; Liu, L.; Chamberlin, T.; Shawler, D.L.; Fakhrai, H. Phase II study of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer. J. Clin. Oncol., 2006, 24, 4721-4730.
163. Viel, T.; Boisgard, R.; Kuhnast, B.; Jego, B.; Siquier-Pernet, K.; Hinnen, F.; Dolle, F.; Tavitian, B. Molecular imaging study on in vivo distribution and pharmacokinetics of modified small interfering RNAs (siRNAs). Oligonucleotides, 2008, 18, 201-212.
164. George, J.; Roulot, D.; Koteliansky, V.E.; Bissell, D.M. In vivo inhibition of rat stellate cell activation by soluble transforming growth factor beta type II receptor: a potential new therapy for hepatic fibrosis. Proc. Natl. Acad. Sci. USA, 1999, 96, 12719-12724.
165. Border, W.A.; Noble, N.A.; Yamamoto, T.; Harper, J.R.; Yamaguchi, Y.; Pierschbacher, M.D.; Ruoslahti, E. Natural inhibitor of transforming growth factor-beta protects against scarring in experimental kidney disease. Nature, 1992, 360, 361-364.
166. Bottinger, E.P.; Factor, V.M.; Tsang, M.L.; Weatherbee, J.A.; Kopp, J.B.; Qian, S.W.; Wakefield, L.M.; Roberts, A.B.; Thorgeirsson, S.S.; Sporn, M.B. The recombinant proregion of transforming growth factor beta1 (latency-associated peptide) inhibits active transforming growth factor beta1 in transgenic mice. Proc. Natl. Acad. Sci. USA, 1996, 93, 5877-5882.
167. Shihab, F.S.; Bennett, W.M.; Yi, H.; Andoh, T.F. Pirfenidone treatment decreases transforming growth factor-beta1 and matrix proteins and ameliorates fibrosis in chronic cyclosporine nephrotoxicity. Am. J. Transplant., 2002, 2, 111-119.
168. Shihab, F.S.; Bennett, W.M.; Yi, H.; Andoh, T.F. Effect of pirfenidone on apoptosis-regulatory genes in chronic cyclosporine nephrotoxicity. Transplantation, 2005, 79, 419-426.
169. Raghu, G.; Johnson, W.C.; Lockhart, D.; Mageto, Y. Treatment of idiopathic pulmonary fibrosis with a new antifibrotic agent, pirfenidone: results of a prospective, open-label Phase II study. Am. J. Respir. Crit. Care Med., 1999, 159, 1061-1069.
170. Kelly, D.J.; Zhang, Y.; Cox, A.J.; Gilbert, R.E. Combination therapy with tranilast and angiotensin-converting enzyme inhibition provides additional renoprotection in the remnant kidney model. Kidney Int., 2006, 69, 1954-1960.
171. Kelly, D.J.; Zhang, Y.; Gow, R.; Gilbert, R.E. Tranilast attenuates structural and functional aspects of renal injury in the remnant kidney model. J. Am. Soc. Nephrol., 2004, 15, 2619-2629.
172. Miyajima, A.; Asano, T.; Asano, T.; Yoshimura, I.; Seta, K.; Hayakawa, M. Tranilast ameliorates renal tubular damage in unilateral ureteral obstruction. J. Urol., 2001, 165, 1714-1718.
173. Qi, W.; Chen, X.; Twigg, S.; Polhill, T.S.; Gilbert, R.E.; Pollock, C.A. Tranilast attenuates connective tissue growth factor-induced extracellular matrix accumulation in renal cells. Kidney Int., 2006, 69, 989-995.
174. Soma, J.; Sugawara, T.; Huang, Y.D.; Nakajima, J.; Kawamura, M. Tranilast slows the progression of advanced diabetic nephropathy. Nephron, 2002, 92, 693-698.
175. Samuel, C.S.; Zhao, C.; Bathgate, R.A.; Du, X.J.; Summers, R.J.; Amento, E.P.; Walker, L.L.; McBurnie, M.; Zhao, L.; Tregear, G.W. The relaxin gene-knockout mouse: a model of progressive fibrosis. Ann. N. Y. Acad. Sci., 2005, 1041, 173-181.
176. Garber, S.L.; Mirochnik, Y.; Brecklin, C.S.; Unemori, E.N.; Singh, A.K.; Slobodskoy, L.; Grove, B.H.; Arruda, J.A.; Dunea, G. Relaxin decreases renal interstitial fibrosis and slows progression of renal disease. Kidney Int., 2001, 59, 876-882.
177. Oikawa, T.; Freeman, M.; Lo, W.; Vaughan, D.E.; Fogo, A. Modulation of plasminogen activator inhibitor-1 in vivo: a new mechanism for the anti-fibrotic effect of renin-angiotensin inhibition. Kidney Int., 1997, 51, 164-172.
178. Nishida, M.; Fujinaka, H.; Matsusaka, T.; Price, J.; Kon, V.; Fogo, A.B.; Davidson, J.M.; Linton, M.F.; Fazio, S.; Homma, T.; Yoshida, H.; Ichikawa, I. Absence of angiotensin II type 1 receptor in bone marrow-derived cells is detrimental in the evolution of renal fibrosis. J. Clin. Invest., 2002, 110, 1859-1868.
179. Frantz, S.; Hu, K.; Adamek, A.; Wolf, J.; Sallam, A.; Maier, S. K.; Lonning, S.; Ling, H.; Ertl, G.; Bauersachs, J. Transforming growth factor beta inhibition increases mortality and left ventricular dilatation after myocardial infarction. Basic Res. Cardiol., 2008, 103, 485-492.
180. Khanna, A.K.; Plummer, M.S.; Hilton, G.; Pieper, G.M.; Ledbetter, S. Anti-transforming growth factor antibody at low but not high doses limits cyclosporine-mediated nephrotoxicity without altering rat cardiac allograft survival: potential of therapeutic applications. Circulation, 2004, 110, 3822-3829.