• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Jun 1986; 83(12): 4167–4171.
PMCID: PMC323692

Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro.

Abstract

Transforming growth factor type beta (TGF-beta), when injected subcutaneously in newborn mice, causes formation of granulation tissue (induction of angiogenesis and activation of fibroblasts to produce collagen) at the site of injection. These effects occur within 2-3 days at dose levels than 1 microgram. Parallel in vitro studies show that TGF-beta causes marked increase of either proline or leucine incorporation into collagen in either an NRK rat fibroblast cell line or early passage human dermal fibroblasts. Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) do not cause these same in vivo and in vitro effects; in both rat and human fibroblast cultures, EGF antagonizes the effects of TGF-beta on collagen formation. We have obtained further data to support a role for TGF-beta as an intrinsic mediator of collagen formation: conditioned media obtained from activated human tonsillar T lymphocytes contain greatly elevated levels of TGF-beta compared to media obtained from unactivated lymphocytes. These activated media markedly stimulate proline incorporation into collagen in NRK cells; this effect is blocked by a specific antibody to TGF-beta. The data are all compatible with the hypothesis that TGF-beta is an important mediator 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 (1.5M), 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

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Roberts AB, Anzano MA, Lamb LC, Smith JM, Sporn MB. New class of transforming growth factors potentiated by epidermal growth factor: isolation from non-neoplastic tissues. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5339–5343. [PMC free article] [PubMed]
  • Roberts AB, Frolik CA, Anzano MA, Sporn MB. Transforming growth factors from neoplastic and nonneoplastic tissues. Fed Proc. 1983 Jun;42(9):2621–2626. [PubMed]
  • Anzano MA, Roberts AB, Smith JM, Sporn MB, De Larco JE. Sarcoma growth factor from conditioned medium of virally transformed cells is composed of both type alpha and type beta transforming growth factors. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6264–6268. [PMC free article] [PubMed]
  • Childs CB, Proper JA, Tucker RF, Moses HL. Serum contains a platelet-derived transforming growth factor. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5312–5316. [PMC free article] [PubMed]
  • Assoian RK, Komoriya A, Meyers CA, Miller DM, Sporn MB. Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. J Biol Chem. 1983 Jun 10;258(11):7155–7160. [PubMed]
  • Frolik CA, Dart LL, Meyers CA, Smith DM, Sporn MB. Purification and initial characterization of a type beta transforming growth factor from human placenta. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3676–3680. [PMC free article] [PubMed]
  • Roberts AB, Anzano MA, Meyers CA, Wideman J, Blacher R, Pan YC, Stein S, Lehrman SR, Smith JM, Lamb LC, et al. Purification and properties of a type beta transforming growth factor from bovine kidney. Biochemistry. 1983 Dec 6;22(25):5692–5698. [PubMed]
  • Derynck R, Jarrett JA, Chen EY, Eaton DH, Bell JR, Assoian RK, Roberts AB, Sporn MB, Goeddel DV. Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells. Nature. 1985 Aug 22;316(6030):701–705. [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]
  • Lawrence WT, Norton JA, Sporn MB, Gorschboth C, Grotendorst GR. The reversal of an Adriamycin induced healing impairment with chemoattractants and growth factors. Ann Surg. 1986 Feb;203(2):142–147. [PMC free article] [PubMed]
  • Johnson RL, Ziff M. Lymphokine stimulation of collagen accumulation. J Clin Invest. 1976 Jul;58(1):240–252. [PMC free article] [PubMed]
  • Kondo H, Rabin BS, Rodnan GP. Cutaneous antigen-stimulating lymphokine production by lymphocytes of patients with progressive systemic sclerosis (scleroderma). J Clin Invest. 1976 Dec;58(6):1388–1394. [PMC free article] [PubMed]
  • Sporn MB, Harris ED., Jr Proliferative diseases. Am J Med. 1981 Jun;70(6):1231–1235. [PubMed]
  • Postlethwaite AE, Smith GN, Mainardi CL, Seyer JM, Kang AH. Lymphocyte modulation of fibroblast function in vitro: stimulation and inhibition of collagen production by different effector molecules. J Immunol. 1984 May;132(5):2470–2477. [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]
  • Frolik CA, Wakefield LM, Smith DM, Sporn MB. Characterization of a membrane receptor for transforming growth factor-beta in normal rat kidney fibroblasts. J Biol Chem. 1984 Sep 10;259(17):10995–11000. [PubMed]
  • Boerner P, Resnick RJ, Racker E. Stimulation of glycolysis and amino acid uptake in NRK-49F cells by transforming growth factor beta and epidermal growth factor. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1350–1353. [PMC free article] [PubMed]
  • Goding JW. Use of staphylococcal protein A as an immunological reagent. J Immunol Methods. 1978;20:241–253. [PubMed]
  • COHEN S. Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J Biol Chem. 1962 May;237:1555–1562. [PubMed]
  • Smith JM, Sporn MB, Roberts AB, Derynck R, Winkler ME, Gregory H. Human transforming growth factor-alpha causes precocious eyelid opening in newborn mice. Nature. 1985 Jun 6;315(6019):515–516. [PubMed]
  • Racker E, Resnick RJ, Feldman R. Glycolysis and methylaminoisobutyrate uptake in rat-1 cells transfected with ras or myc oncogenes. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3535–3538. [PMC free article] [PubMed]
  • Boerner P, Saier MH., Jr Growth regulation and amino acid transport in epithelial cells: influence of culture conditions and transformation on A, ASC, and L transport activities. J Cell Physiol. 1982 Nov;113(2):240–246. [PubMed]
  • Carpenter G, Cohen S. Epidermal growth factor. Annu Rev Biochem. 1979;48:193–216. [PubMed]
  • Hollenberg MD, Cuatrecasas P. Insulin and epidermal growth factor. Human fibroblast receptors related to deoxyribonucleic acid synthesis and amino acid uptake. J Biol Chem. 1975 May 25;250(10):3845–3853. [PubMed]
  • Krycève-Martinerie C, Lawrence DA, Crochet J, Jullien P, Vigier P. Further study of beta-TGFs released by virally transformed and non-transformed cells. Int J Cancer. 1985 Apr 15;35(4):553–558. [PubMed]
  • Folkman J, Cotran R. Relation of vascular proliferation to tumor growth. Int Rev Exp Pathol. 1976;16:207–248. [PubMed]
  • Maciag T. Angiogenesis. Prog Hemost Thromb. 1984;7:167–182. [PubMed]
  • Esch F, Baird A, Ling N, Ueno N, Hill F, Denoroy L, Klepper R, Gospodarowicz D, Böhlen P, Guillemin R. Primary structure of bovine pituitary basic fibroblast growth factor (FGF) and comparison with the amino-terminal sequence of bovine brain acidic FGF. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6507–6511. [PMC free article] [PubMed]
  • Lobb RR, Alderman EM, Fett JW. Induction of angiogenesis by bovine brain derived class 1 heparin-binding growth factor. Biochemistry. 1985 Sep 10;24(19):4969–4973. [PubMed]
  • Fett JW, Strydom DJ, Lobb RR, Alderman EM, Bethune JL, Riordan JF, Vallee BL. Isolation and characterization of angiogenin, an angiogenic protein from human carcinoma cells. Biochemistry. 1985 Sep 24;24(20):5480–5486. [PubMed]
  • Pierschbacher MD, Ruoslahti E. Variants of the cell recognition site of fibronectin that retain attachment-promoting activity. Proc Natl Acad Sci U S A. 1984 Oct;81(19):5985–5988. [PMC free article] [PubMed]
  • Assoian RK, Grotendorst GR, Miller DM, Sporn MB. Cellular transformation by coordinated action of three peptide growth factors from human platelets. Nature. 309(5971):804–806. [PubMed]
  • Shimokado K, Raines EW, Madtes DK, Barrett TB, Benditt EP, Ross R. A significant part of macrophage-derived growth factor consists of at least two forms of PDGF. Cell. 1985 Nov;43(1):277–286. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • OMIM
    OMIM
    OMIM record citing PubMed
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...