• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Jul 1992; 90(1): 1–7.
PMCID: PMC443055

Transforming growth factor-beta in disease: the dark side of tissue repair.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Sporn MB, Roberts AB. TGF-beta: problems and prospects. Cell Regul. 1990 Nov;1(12):875–882. [PMC free article] [PubMed]
  • Barnard JA, Lyons RM, Moses HL. The cell biology of transforming growth factor beta. Biochim Biophys Acta. 1990 Jun 1;1032(1):79–87. [PubMed]
  • Assoian RK, Sporn MB. Type beta transforming growth factor in human platelets: release during platelet degranulation and action on vascular smooth muscle cells. J Cell Biol. 1986 Apr;102(4):1217–1223. [PMC free article] [PubMed]
  • Wahl SM, Hunt DA, Wakefield LM, McCartney-Francis N, Wahl LM, Roberts AB, Sporn MB. Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5788–5792. [PMC free article] [PubMed]
  • Postlethwaite AE, Keski-Oja J, Moses HL, Kang AH. Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta. J Exp Med. 1987 Jan 1;165(1):251–256. [PMC free article] [PubMed]
  • Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH, et al. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4167–4171. [PMC free article] [PubMed]
  • Kehrl JH, Wakefield LM, Roberts AB, Jakowlew S, Alvarez-Mon M, Derynck R, Sporn MB, Fauci AS. Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth. J Exp Med. 1986 May 1;163(5):1037–1050. [PMC free article] [PubMed]
  • Ristow HJ. BSC-1 growth inhibitor/type beta transforming growth factor is a strong inhibitor of thymocyte proliferation. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5531–5533. [PMC free article] [PubMed]
  • Tsunawaki S, Sporn M, Ding A, Nathan C. Deactivation of macrophages by transforming growth factor-beta. Nature. 1988 Jul 21;334(6179):260–262. [PubMed]
  • Kim SJ, Jeang KT, Glick AB, Sporn MB, Roberts AB. Promoter sequences of the human transforming growth factor-beta 1 gene responsive to transforming growth factor-beta 1 autoinduction. J Biol Chem. 1989 Apr 25;264(12):7041–7045. [PubMed]
  • Sporn MB, Roberts AB, Shull JH, Smith JM, Ward JM, Sodek J. Polypeptide transforming growth factors isolated from bovine sources and used for wound healing in vivo. Science. 1983 Mar 18;219(4590):1329–1331. [PubMed]
  • Balza E, Borsi L, Allemanni G, Zardi L. Transforming growth factor beta regulates the levels of different fibronectin isoforms in normal human cultured fibroblasts. FEBS Lett. 1988 Feb 8;228(1):42–44. [PubMed]
  • Wang A, Cohen DS, Palmer E, Sheppard D. Polarized regulation of fibronectin secretion and alternative splicing by transforming growth factor. J Biol Chem. 1991 Aug 25;266(24):15598–15601. [PubMed]
  • Ignotz RA, Massagué J. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem. 1986 Mar 25;261(9):4337–4345. [PubMed]
  • Bassols A, Massagué J. Transforming growth factor beta regulates the expression and structure of extracellular matrix chondroitin/dermatan sulfate proteoglycans. J Biol Chem. 1988 Feb 25;263(6):3039–3045. [PubMed]
  • Pearson CA, Pearson D, Shibahara S, Hofsteenge J, Chiquet-Ehrismann R. Tenascin: cDNA cloning and induction by TGF-beta. EMBO J. 1988 Oct;7(10):2977–2982. [PMC free article] [PubMed]
  • Edwards DR, Murphy G, Reynolds JJ, Whitham SE, Docherty AJ, Angel P, Heath JK. Transforming growth factor beta modulates the expression of collagenase and metalloproteinase inhibitor. EMBO J. 1987 Jul;6(7):1899–1904. [PMC free article] [PubMed]
  • Laiho M, Saksela O, Keski-Oja J. Transforming growth factor-beta induction of type-1 plasminogen activator inhibitor. Pericellular deposition and sensitivity to exogenous urokinase. J Biol Chem. 1987 Dec 25;262(36):17467–17474. [PubMed]
  • Ignotz RA, Massagué J. Cell adhesion protein receptors as targets for transforming growth factor-beta action. Cell. 1987 Oct 23;51(2):189–197. [PubMed]
  • Okuda S, Languino LR, Ruoslahti E, Border WA. Elevated expression of transforming growth factor-beta and proteoglycan production in experimental glomerulonephritis. Possible role in expansion of the mesangial extracellular matrix. J Clin Invest. 1990 Aug;86(2):453–462. [PMC free article] [PubMed]
  • Vassalli JD, Sappino AP, Belin D. The plasminogen activator/plasmin system. J Clin Invest. 1991 Oct;88(4):1067–1072. [PMC free article] [PubMed]
  • Pöllänen J, Hedman K, Nielsen LS, Danø K, Vaheri A. Ultrastructural localization of plasma membrane-associated urokinase-type plasminogen activator at focal contacts. J Cell Biol. 1988 Jan;106(1):87–95. [PMC free article] [PubMed]
  • Border WA, Okuda S, Languino LR, Sporn MB, Ruoslahti E. Suppression of experimental glomerulonephritis by antiserum against transforming growth factor beta 1. Nature. 1990 Jul 26;346(6282):371–374. [PubMed]
  • Yamaguchi Y, Mann DM, Ruoslahti E. Negative regulation of transforming growth factor-beta by the proteoglycan decorin. Nature. 1990 Jul 19;346(6281):281–284. [PubMed]
  • Coimbra T, Wiggins R, Noh JW, Merritt S, Phan SH. Transforming growth factor-beta production in anti-glomerular basement membrane disease in the rabbit. Am J Pathol. 1991 Jan;138(1):223–234. [PMC free article] [PubMed]
  • Downer G, Phan SH, Wiggins RC. Analysis of renal fibrosis in a rabbit model of crescentic nephritis. J Clin Invest. 1988 Sep;82(3):998–1006. [PMC free article] [PubMed]
  • Velasquez MT, Kimmel PL, Michaelis OE., 4th Animal models of spontaneous diabetic kidney disease. FASEB J. 1990 Aug;4(11):2850–2859. [PubMed]
  • Mauer SM, Steffes MW, Ellis EN, Sutherland DE, Brown DM, Goetz FC. Structural-functional relationships in diabetic nephropathy. J Clin Invest. 1984 Oct;74(4):1143–1155. [PMC free article] [PubMed]
  • Bohle A, Mackensen-Haen S, von Gise H. Significance of tubulointerstitial changes in the renal cortex for the excretory function and concentration ability of the kidney: a morphometric contribution. Am J Nephrol. 1987;7(6):421–433. [PubMed]
  • Myers BD, Ross J, Newton L, Luetscher J, Perlroth M. Cyclosporine-associated chronic nephropathy. N Engl J Med. 1984 Sep 13;311(11):699–705. [PubMed]
  • Shah M, Foreman DM, Ferguson MW. Control of scarring in adult wounds by neutralising antibody to transforming growth factor beta. Lancet. 1992 Jan 25;339(8787):213–214. [PubMed]
  • Broekelmann TJ, Limper AH, Colby TV, McDonald JA. Transforming growth factor beta 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6642–6646. [PMC free article] [PubMed]
  • Raghow B, Irish P, Kang AH. Coordinate regulation of transforming growth factor beta gene expression and cell proliferation in hamster lungs undergoing bleomycin-induced pulmonary fibrosis. J Clin Invest. 1989 Dec;84(6):1836–1842. [PMC free article] [PubMed]
  • Castilla A, Prieto J, Fausto N. Transforming growth factors beta 1 and alpha in chronic liver disease. Effects of interferon alfa therapy. N Engl J Med. 1991 Apr 4;324(14):933–940. [PubMed]
  • Czaja MJ, Weiner FR, Flanders KC, Giambrone MA, Wind R, Biempica L, Zern MA. In vitro and in vivo association of transforming growth factor-beta 1 with hepatic fibrosis. J Cell Biol. 1989 Jun;108(6):2477–2482. [PMC free article] [PubMed]
  • Thompson NL, Bazoberry F, Speir EH, Casscells W, Ferrans VJ, Flanders KC, Kondaiah P, Geiser AG, Sporn MB. Transforming growth factor beta-1 in acute myocardial infarction in rats. Growth Factors. 1988;1(1):91–99. [PubMed]
  • Connor TB, Jr, Roberts AB, Sporn MB, Danielpour D, Dart LL, Michels RG, de Bustros S, Enger C, Kato H, Lansing M, et al. Correlation of fibrosis and transforming growth factor-beta type 2 levels in the eye. J Clin Invest. 1989 May;83(5):1661–1666. [PMC free article] [PubMed]
  • Gruschwitz M, Müller PU, Sepp N, Hofer E, Fontana A, Wick G. Transcription and expression of transforming growth factor type beta in the skin of progressive systemic sclerosis: a mediator of fibrosis? J Invest Dermatol. 1990 Feb;94(2):197–203. [PubMed]
  • Kulozik M, Hogg A, Lankat-Buttgereit B, Krieg T. Co-localization of transforming growth factor beta 2 with alpha 1(I) procollagen mRNA in tissue sections of patients with systemic sclerosis. J Clin Invest. 1990 Sep;86(3):917–922. [PMC free article] [PubMed]
  • Peltonen J, Varga J, Sollberg S, Uitto J, Jimenez SA. Elevated expression of the genes for transforming growth factor-beta 1 and type VI collagen in diffuse fasciitis associated with the eosinophilia-myalgia syndrome. J Invest Dermatol. 1991 Jan;96(1):20–25. [PubMed]
  • Williams RS, Rossi AM, Chegini N, Schultz G. Effect of transforming growth factor beta on postoperative adhesion formation and intact peritoneum. J Surg Res. 1992 Jan;52(1):65–70. [PubMed]
  • Whitby DJ, Ferguson MW. Immunohistochemical localization of growth factors in fetal wound healing. Dev Biol. 1991 Sep;147(1):207–215. [PubMed]
  • Hermans WR, Rensing BJ, Strauss BH, Serruys PW. Prevention of restenosis after percutaneous transluminal coronary angioplasty: the search for a "magic bullet". Am Heart J. 1991 Jul;122(1 Pt 1):171–187. [PubMed]
  • Macdonald RG, Henderson MA, Hirshfeld JW, Jr, Goldberg SH, Bass T, Vetrovec G, Cowley M, Taussig A, Whitworth H, Margolis JR, et al. Patient-related variables and restenosis after percutaneous transluminal coronary angioplasty--a report from the M-HEART Group. Am J Cardiol. 1990 Oct 15;66(12):926–931. [PubMed]
  • Nobuyoshi M, Kimura T, Ohishi H, Horiuchi H, Nosaka H, Hamasaki N, Yokoi H, Kim K. Restenosis after percutaneous transluminal coronary angioplasty: pathologic observations in 20 patients. J Am Coll Cardiol. 1991 Feb;17(2):433–439. [PubMed]
  • Majesky MW, Lindner V, Twardzik DR, Schwartz SM, Reidy MA. Production of transforming growth factor beta 1 during repair of arterial injury. J Clin Invest. 1991 Sep;88(3):904–910. [PMC free article] [PubMed]
  • Sarzani R, Brecher P, Chobanian AV. Growth factor expression in aorta of normotensive and hypertensive rats. J Clin Invest. 1989 Apr;83(4):1404–1408. [PMC free article] [PubMed]
  • Kurihara H, Yoshizumi M, Sugiyama T, Takaku F, Yanagisawa M, Masaki T, Hamaoki M, Kato H, Yazaki Y. Transforming growth factor-beta stimulates the expression of endothelin mRNA by vascular endothelial cells. Biochem Biophys Res Commun. 1989 Mar 31;159(3):1435–1440. [PubMed]
  • Brown MR, Vaughan J, Jimenez LL, Vale W, Baird A. Transforming growth factor-beta: role in mediating serum-induced endothelin production by vascular endothelial cells. Endocrinology. 1991 Nov;129(5):2355–2360. [PubMed]
  • Terui T, Niitsu Y, Mahara K, Fujisaki Y, Urushizaki Y, Mogi Y, Kohgo Y, Watanabe N, Ogura M, Saito H. The production of transforming growth factor-beta in acute megakaryoblastic leukemia and its possible implications in myelofibrosis. Blood. 1990 Apr 1;75(7):1540–1548. [PubMed]
  • Sieweke MH, Thompson NL, Sporn MB, Bissell MJ. Mediation of wound-related Rous sarcoma virus tumorigenesis by TGF-beta. Science. 1990 Jun 29;248(4963):1656–1660. [PubMed]
  • Akhurst RJ, Fee F, Balmain A. Localized production of TGF-beta mRNA in tumour promoter-stimulated mouse epidermis. Nature. 1988 Jan 28;331(6154):363–365. [PubMed]
  • Brandes ME, Allen JB, Ogawa Y, Wahl SM. Transforming growth factor beta 1 suppresses acute and chronic arthritis in experimental animals. J Clin Invest. 1991 Mar;87(3):1108–1113. [PMC free article] [PubMed]
  • Kuruvilla AP, Shah R, Hochwald GM, Liggitt HD, Palladino MA, Thorbecke GJ. Protective effect of transforming growth factor beta 1 on experimental autoimmune diseases in mice. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2918–2921. [PMC free article] [PubMed]
  • Allen JB, Manthey CL, Hand AR, Ohura K, Ellingsworth L, Wahl SM. Rapid onset synovial inflammation and hyperplasia induced by transforming growth factor beta. J Exp Med. 1990 Jan 1;171(1):231–247. [PMC free article] [PubMed]
  • van Vlasselaer P, Punnonen J, de Vries JE. Transforming growth factor-beta directs IgA switching in human B cells. J Immunol. 1992 Apr 1;148(7):2062–2067. [PubMed]
  • Rodicio JL. Idiopathic IgA nephropathy. Kidney Int. 1984 Apr;25(4):717–729. [PubMed]
  • Bene MC, Faure G, Hurault de Ligny B, Kessler M, Duheille J. Immunoglobulin A nephropathy. Quantitative immunohistomorphometry of the tonsillar plasma cells evidences an inversion of the immunoglobulin A versus immunoglobulin G secreting cell balance. J Clin Invest. 1983 May;71(5):1342–1347. [PMC free article] [PubMed]
  • O'Donoghue DJ, Darvill A, Ballardie FW. Mesangial cell autoantigens in immunoglobulin A nephropathy and Henoch-Schönlein purpura. J Clin Invest. 1991 Nov;88(5):1522–1530. [PMC free article] [PubMed]
  • Kekow J, Wachsman W, McCutchan JA, Gross WL, Zachariah M, Carson DA, Lotz M. Transforming growth factor-beta and suppression of humoral immune responses in HIV infection. J Clin Invest. 1991 Mar;87(3):1010–1016. [PMC free article] [PubMed]
  • Kekow J, Wachsman W, McCutchan JA, Cronin M, Carson DA, Lotz M. Transforming growth factor beta and noncytopathic mechanisms of immunodeficiency in human immunodeficiency virus infection. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8321–8325. [PMC free article] [PubMed]
  • Rao TK, Filippone EJ, Nicastri AD, Landesman SH, Frank E, Chen CK, Friedman EA. Associated focal and segmental glomerulosclerosis in the acquired immunodeficiency syndrome. N Engl J Med. 1984 Mar 15;310(11):669–673. [PubMed]
  • Kopp JB, Klotman ME, Adler SH, Bruggeman LA, Dickie P, Marinos NJ, Eckhaus M, Bryant JL, Notkins AL, Klotman PE. Progressive glomerulosclerosis and enhanced renal accumulation of basement membrane components in mice transgenic for human immunodeficiency virus type 1 genes. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1577–1581. [PMC free article] [PubMed]
  • Lafyatis R, Denhez F, Williams T, Sporn M, Roberts A. Sequence specific protein binding to and activation of the TGF-beta 3 promoter through a repeated TCCC motif. Nucleic Acids Res. 1991 Dec 11;19(23):6419–6425. [PMC free article] [PubMed]
  • Van Obberghen-Schilling E, Roche NS, Flanders KC, Sporn MB, Roberts AB. Transforming growth factor beta 1 positively regulates its own expression in normal and transformed cells. J Biol Chem. 1988 Jun 5;263(16):7741–7746. [PubMed]
  • Lyons RM, Moses HL. Transforming growth factors and the regulation of cell proliferation. Eur J Biochem. 1990 Feb 14;187(3):467–473. [PubMed]
  • Huber D, Philipp J, Fontana A. Protease inhibitors interfere with the transforming growth factor-beta-dependent but not the transforming growth factor-beta-independent pathway of tumor cell-mediated immunosuppression. J Immunol. 1992 Jan 1;148(1):277–284. [PubMed]
  • Gentry LE, Webb NR, Lim GJ, Brunner AM, Ranchalis JE, Twardzik DR, Lioubin MN, Marquardt H, Purchio AF. Type 1 transforming growth factor beta: amplified expression and secretion of mature and precursor polypeptides in Chinese hamster ovary cells. Mol Cell Biol. 1987 Oct;7(10):3418–3427. [PMC free article] [PubMed]
  • Wakefield LM, Smith DM, Broz S, Jackson M, Levinson AD, Sporn MB. Recombinant TGF-beta 1 is synthesized as a two-component latent complex that shares some structural features with the native platelet latent TGF-beta 1 complex. Growth Factors. 1989;1(3):203–218. [PubMed]
  • Gentry LE, Nash BW. The pro domain of pre-pro-transforming growth factor beta 1 when independently expressed is a functional binding protein for the mature growth factor. Biochemistry. 1990 Jul 24;29(29):6851–6857. [PubMed]
  • López-Casillas F, Cheifetz S, Doody J, Andres JL, Lane WS, Massagué J. Structure and expression of the membrane proteoglycan betaglycan, a component of the TGF-beta receptor system. Cell. 1991 Nov 15;67(4):785–795. [PubMed]
  • Wang XF, Lin HY, Ng-Eaton E, Downward J, Lodish HF, Weinberg RA. Expression cloning and characterization of the TGF-beta type III receptor. Cell. 1991 Nov 15;67(4):797–805. [PubMed]
  • Lin HY, Wang XF, Ng-Eaton E, Weinberg RA, Lodish HF. Expression cloning of the TGF-beta type II receptor, a functional transmembrane serine/threonine kinase. Cell. 1992 Feb 21;68(4):775–785. [PubMed]
  • Wakefield L, Kim SJ, Glick A, Winokur T, Colletta A, Sporn M. Regulation of transforming growth factor-beta subtypes by members of the steroid hormone superfamily. J Cell Sci Suppl. 1990;13:139–148. [PubMed]
  • Okuda S, Nakamura T, Yamamoto T, Ruoslahti E, Border WA. Dietary protein restriction rapidly reduces transforming growth factor beta 1 expression in experimental glomerulonephritis. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9765–9769. [PMC free article] [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Compound
    PubChem Compound links
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...