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Instituto Nacional de Salud Pública

2004, Número 4

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salud publica mex 2004; 46 (4)


El factor de crecimiento transformanteβ como blanco terapéutico

Gálvez-Gastélum FJ, Sandoval-Rodríguez AS, Armendáriz-Borunda J

Idioma: Español
Referencias bibliográficas: 81
Paginas: 341-350
Archivo PDF: 173.87 Kb.


RESUMEN

El factor de crecimiento transformante β (TGF-β) es una familia de proteínas que incluye al TGF-β, activinas y a la proteína morfogénica de hueso (BMP, por sus siglas en inglés), citocinas que son secretadas y se relacionan estructuralmente en diferentes especies de metazoarios. Los miembros de la familia del TGF-β regulan diferentes funciones celulares como proliferación, apoptosis, diferenciación, migración, y tienen un papel clave en el desarrollo del organismo. El TGF-β está implicado en varias patologías humanas, incluyendo desórdenes autoinmunes y vasculares, así como enfermedades fibróticas y cáncer. La activación del receptor del TGF-β propicia su fosforilación en residuos de serina/treonina y dispara la fosforilación de proteínas efectoras intracelulares (smad), que una vez activas se transcan al núcleo para inducir la transcripción de genes blanco, y así regular procesos y funciones celulares. Se están desarrollando novedosas estrategias terapéuticas encaminadas a corregir las alteraciones presentes en patologías que involucran al TGF-β como actor principal.


REFERENCIAS (EN ESTE ARTÍCULO)

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  2. Zhu H, Burgess A. Regulation of transforming growth factor B signaling. Mol Cell Biol Res Community 2001;4:321-330.

  3. Miyazono K. Positive and negative regulation ofTGF/3 signaling.J Cell Sci 2000;1 13:1 101-1 109.

  4. Peralta-Zaragoza O, Lagunas-Martínez A, Madrid-Marina V. Transforming growth factor beta-1: Structure, function, and regulation mechanisms in cancer. Salud Publica Mex 2001;43:340-351.salud pública de méxico / vol.46, no.4, julio-agosto de 2004

  5. Border W, Noble N.TGF-/3. Sci Am Sci Med 1995;2:68-77.

  6. Bissell M, Roulot D, George J.Transforming growth factor and the liver. Hepatology 2001;34:859-867.

  7. Hernández-Cañaveral I, González J, López-Casillas F,Armendáriz-Borunda J. Amplified expression of dominant-negative transforming growth factor-beta type 11 receptor inhibits collagen type 1 production via reduced Smad-3 activity.J Gastroenterol Hepatol 2004;19:380-387.

  8. Caestecker M.The transforming growth factor-B superfamily of receptors. Cytokine Growth Factor Rev 2004;15:1-11.

  9. Kondou H, Mushiake S, Etani Y, Moyoshi Y, Michigami T, Ozono K.A blocking peptide for transforming growth factor-B I activation prevents hepatic fibrosis

  10. Susumu I, Fumiko 1, Goumans M, Dijke T. Signaling of transforming growth factor-B family members through Smad proteins. Eur J Biochem 2000;267:6954-6967.

  11. Heldin CH, Miyazono J, Dijke P.TGF-/3 signaling from cell membrane to nucleus through SMAD proteins. Nature 1997;390:465-471.

  12. Roberts A.TGF-/3 signaling from receptors to the nucleus, Microbes Infect 1999;1:1265-1273.

  13. Derynck R, Zhang Y. Smad-dependent and smad-independent pathways in TGF-/3 family signaling. Nature 2003;425:577-584.

  14. 15.Whitman M. Feedback from inhibitory SMADs. Nature 1997;389:549-551.

  15. Dijke Pt, Miyazono K, CH H. Signalling inputs converge on nuclear effectors in TGF-/3 signaling. Trends Biochem Sci 2000;25:64-70.

  16. Moustakas A, Pardali K, Gaal A, Heldin CH. Mechanism ofTGF-/3 signaling in regulation of cell growth and differentiation. Immunol Lett 2002;82:85-91.

  17. Lijnen P, Petrov V, Fagard R. Association between transforming growth factor-B and hypertension. Am J Hypertens 2003;16:604-611.

  18. 19.Armendáriz-Borunda J, LeGros L, Campollo O, Panduro A, Rincón A. Antisense S-oligodeoxynucleotides down-regulate TGFB-production by Kupffer cells from CCL4-injured rat livers. Biochim Biophys Acta 1997;1353:241-252.

  19. Delgado-Rizo V, Salazar A, Panduro A,Armendáriz-Borunda J. Treatment with anti-tumor growth factor B antibodies influences an altered pattern of cytokines gene expression in injured rat liver. Biochim Biophys Acta 1998; vol 1442(I):20-27.

  20. GressnerA,Weiskirchen R, Breitkopf K, Dooley S. Roles ofTGF-/3 in hepatic fibrosis. Front Biosci 2002;7:793-807.

  21. Okuno M,Akita K, Moriwaki H, Kawada N, Ikeda K, Kaneda K et al. Prevention of rat hepatic fibrosis by the protease inhibitor, camostat mesilate, via reduced generation of active TGF-/3. Gastroenterology 2001;120:1781-1800.

  22. Dooley S, Hamzavi J, Breitkopf K, Wiercinska E, Said H, Lorenzen J

  23. 24.Arias M, Sauer-Lehnen S,Treptau J,Janoschek N,Theuerkauf I, Buettner R et

  24. 25.YataY, Gotwals P, KoteianskyV, Rockey D. Dose-dependent inhibition of hepatic fibrosis in mice by aTGF-/3 soluble receptor: Implications for antifibrotic therapy. Hepatology 2002;35:1022-1030.

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  28. Siegel P, Massague J. Cytostatic and apoptotic actions ofTGF-/3 in homeostasis and cancer. Nature Rev Cancer 2003;3:807-817.

  29. Ignotz R, Honeyman T.TGF-/3 signaling in A549 lung carcinoma cells: Lipid second messengers. J Cell Biochem 2000;78:588-594.

  30. Duda D, Sunamura M, Lefler L, Furukawa T,Yokoyama T,Yatsuoka T et

  31. Moira K. Genetic factors in idiopathic pulmonary fibrosis: Transforming growth factor-B implicated at last. Am J Respir Crit Care Med 2003;168:410-411.

  32. Warshamana GDP, Fisher K, Liu J, Sime P, Brody A.Titration of non-replicating adenovirus as a vector for transducing active TGF-/3l gene expression causing inflammation and fibrigenesis in the lungs of C57BL/ 6 mice. Inc J Exp Pathol 2002;83:183-201.

  33. Kenyon N,Ward R, McGrew G, Last J.TGF-/31 causes airway fibrosis and increased collagen I and Ill mRNA in mice. Thorax 2003;58:772-777.

  34. Nakao A, Fujii M, Matsumura R, Kumano K, Saito Y, Mlyazono K et

  35. Rabbani Z,Anscher M, Zhang X, Chen L, Samulski T, Li C et al. Soluble TGF-/3 type II receptor gene therapy ameliorates acute radiation-induced pulmonary injury in rats. Int J Radiat Oncol Biol Phys 2003;57:563-572.

  36. Chen S, Jim B, Ziyadeh F. Diabetic nephropathy and transforming growth factor B:Transforming our view of glomerulosclerosis and fibrosis build-up. Sem Nephrol 2003;23:532-543.

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  38. Sato M, MuragakiY, Saika S, Roberts A, Ooshima A.Targeted disruption of TGF-beta I /Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction.J Clin Invest 2003;1 12:1486-1494.

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  41. in vivo. J Hepatol 2003;39:742-748.et al. Smad-7 prevents activation of hepatic stellate cells and liver fibrosis in rats. Gastroenterology 2003;125:178-191.al.Adenoviral expression of a transforming growth factor B I antisense mRNA is effective in preventing liver fibrosis in bile-duct ligated rats. BMC Gastroenterology 2003;3:1-12.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 Scil USA 1999;96:12719-12724.et al. Gene therapy by transforming growth factor-beta receptor-IgG Fc chimera suppressed extracellular matrix accumulation in experimental glomerulonephritis. Kidney Int 1999;55:465-475.al. Restoration of Smad4 by gene therapy reverses the invasive phenotype in pancreatic adenocarcinoma cells. Oncogene 2003;22:6857-6864.al. Transient gene transfer and expression of Smad 7 prevents bleomycin-induced lung fibrosis in mice. J Clin Invest 1999;104:5-11.al. Antisense oligonucleotides against thrombospondin- I inhibit activation ofTGF-/3 fibrotic renal disease in the rat in vive. Am J Patholal. Inhibiton of transforming growth factor B signaling accelerates atherosclerosis and induces an unstable plaque phenotype in mice. Circ Res 2001;89:930-934.

  42. Blobe G, Schiemman W, Lodish H. Role of transforming growth factor B in human disease. N Engl J Med 2000;4:1350-1358.

  43. Zhu H, Burgess A. Regulation of transforming growth factor B signaling. Mol Cell Biol Res Community 2001;4:321-330.

  44. Miyazono K. Positive and negative regulation ofTGF/3 signaling.J Cell Sci 2000;113:1101-1109.

  45. Peralta-Zaragoza O, Lagunas-Martínez A, Madrid-Marina V. Transforming growth factor beta-1: Structure, function, and regulation mechanisms in cancer. Salud Publica Mex 2001;43:340-351.salud pública de méxico/vol.46, no.4, julio-agosto de 2004

  46. Border W, Noble N.TGF-/3. Sci Am Sci Med 1995;2:68-77.

  47. Bissell M, Roulot D, George J.Transforming growth factor and the liver. Hepatology 2001;34:859-867.

  48. Hernández-Cañaveral I, González J, López-Casillas F,Armendáriz-Borunda J. Amplified expression of dominant-negative transforming growth factor-beta type 11 receptor inhibits collagen type 1 production via reduced Smad-3 activity.J Gastroenterol Hepatol 2004;19:380-387.

  49. Caestecker M.The transforming growth factor-B superfamily of receptors. Cytokine Growth Factor Rev 2004;15:1-11.

  50. Kondou H, Mushiake S, Etani Y, Moyoshi Y, Michigami T, Ozono K.A blocking peptide for transforming growth factor-B I activation prevents hepatic fibrosis

  51. Susumu I, Fumiko I, Goumans M, Dijke T. Signaling of transforming growth factor-B family members through Smad proteins. Eur J Biochem 2000;267:6954-6967.

  52. Heldin CH, Miyazono J, Dijke P.TGF-/3 signaling from cell membrane to nucleus through SMAD proteins. Nature 1997;390:465-471.

  53. Roberts A.TGF-/3 signaling from receptors to the nucleus, Microbes Infect 1999;1:1265-1273.

  54. Derynck R, Zhang Y. Smad-dependent and smad-independent pathways in TGF-/3 family signaling. Nature 2003;425:577-584.

  55. 15.Whitman M. Feedback from inhibitory SMADs. Nature 1997;389:549-551.

  56. Dijke Pt, Miyazono K, CH H. Signalling inputs converge on nuclear effectors in TGF-/3 signaling. Trends Biochem Sci 2000;25:64-70.

  57. Moustakas A, Pardali K, Gaal A, Heldin CH. Mechanism ofTGF-/3 signaling in regulation of cell growth and differentiation. Immunol Lett 2002;82:85-91.

  58. Lijnen P, Petrov V, Fagard R. Association between transforming growth factor-B and hypertension. Am J Hypertens 2003;16:604-611.

  59. 19.Armendáriz-Borunda J, LeGros L, Campollo O, Panduro A, Rincón A. Antisense S-oligodeoxynucleotides down-regulate TGFB-production by Kupffer cells from CCL4-injured rat livers. Biochim Biophys Acta 1997;1353:241-252.

  60. Delgado-Rizo V, Salazar A, Panduro A,Armendáriz-Borunda J. Treatment with anti-tumor growth factor B antibodies influences an altered pattern of cytokines gene expression in injured rat liver. Biochim Biophys Acta 1998; vol 1442(I):20-27.

  61. GressnerA,Weiskirchen R, Breitkopf K, Dooley S. Roles ofTGF-/3 in hepatic fibrosis. Front Biosci 2002;7:793-807.

  62. Okuno M,Akita K, Moriwaki H, Kawada N, Ikeda K, Kaneda K et al. Prevention of rat hepatic fibrosis by the protease inhibitor, camostat mesilate, via reduced generation of active TGF-/3. Gastroenterology 2001;120:1781-1800.

  63. Dooley S, Hamzavi J, Breitkopf K, Wiercinska E, Said H, Lorenzen J

  64. 24.Arias M, Sauer-Lehnen S,Treptau J,Janoschek N,Theuerkauf I, Buettner R et

  65. 25.YataY, Gotwals P, KoteianskyV, Rockey D. Dose-dependent inhibition of hepatic fibrosis in mice by aTGF-/3 soluble receptor: Implications for antifibrotic therapy. Hepatology 2002;35:1022-1030.

  66. George J, Roulot D, KotelianskyV,Vissell D.

  67. Isaka Y,Akagi Y,Ando Y, Tsujie M, Sudo T, Ohno N

  68. Huang X, Lee C. From TGF-/3 to cancer therapy. Curr Drug Targets 2003;4:243-250.

  69. Siegel P, Massague J. Cytostatic and apoptotic actions ofTGF-/3 in homeostasis and cancer. Nature Rev Cancer 2003;3:807-817.

  70. Ignotz R, Honeyman T.TGF-/3 signaling in A549 lung carcinoma cells: Lipid second messengers. J Cell Biochem 2000;78:588-594.

  71. Duda D, Sunamura M, Lefler L, Furukawa T,Yokoyama T,Yatsuoka T et

  72. Moira K. Genetic factors in idiopathic pulmonary fibrosis: Transforming growth factor-B implicated at last. Am J Respir Crit Care Med 2003;168:410-411.

  73. Warshamana GDP, Fisher K, Liu J, Sime P, Brody A.Titration of non-replicating adenovirus as a vector for transducing active TGF-/3l gene expression causing inflammation and fibrigenesis in the lungs of C57BL/6 mice. Inc J Exp Pathol 2002;83:183-201.

  74. Kenyon N,Ward R, McGrew G, Last J.TGF-/31 causes airway fibrosis and increased collagen I and Ill mRNA in mice. Thorax 2003;58:772-777.

  75. Nakao A, Fujii M, Matsumura R, Kumano K, Saito Y, Mlyazono K et

  76. Rabbani Z,Anscher M, Zhang X, Chen L, Samulski T, Li C et al. Soluble TGF-/3 type II receptor gene therapy ameliorates acute radiation-induced pulmonary injury in rats. Int J Radiat Oncol Biol Phys 2003;57:563-572.

  77. Chen S, Jim B, Ziyadeh F. Diabetic nephropathy and transforming growth factor B:Transforming our view of glomerulosclerosis and fibrosis build-up. Sem Nephrol 2003;23:532-543.

  78. Daniel C,TakabatakeY, Mizui M, IsakaY, Kawashi H, Ruppecht H et 2003;163: 1185-1192.

  79. Sato M, MuragakiY, Saika S, Roberts A, Ooshima A.Targeted disruption of TGF-beta I/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction.J Clin Invest 2003;1 12:1486-1494.

  80. Mallat Z, GojovaA, Marchiol-Fournigault C, Esposio B, Kamaté C, Merval R et

  81. Robertson A, Rudling M, Zhu X, Gorelik L, Flavell R, Hansson G. Disruption ofTGF-/3 signaling in T cells accelerates atherosclerosis. J Clin Invest 2003;112:1342-1350.




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