PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jcellbiolHomeEditorsContactInstructions for Authors
 
J Cell Biol. 1986 April 1; 102(4): 1217–1223.
PMCID: PMC2114151

Type beta transforming growth factor in human platelets: release during platelet degranulation and action on vascular smooth muscle cells

Abstract

A specific radioimmunoassay for type beta transforming growth factor (TGF-beta) was developed and used to show that human platelets treated with thrombin release TGF-beta as a consequence of degranulation. The thrombin concentrations required to induce release of TGF-beta parallel those concentrations that release the alpha-granule marker, beta- thromboglobulin. Related studies showed that TGF-beta acts on early passage, explant cultures of bovine aortic smooth muscle cells by inhibiting the effect of mitogens on proliferation of subconfluent cell monolayers yet synergizing with mitogens to stimulate growth of the same cells when cultured in soft agar. The results show that primary cultures of bovine aortic smooth muscle cells and established normal rat kidney cells behave similarly with regard to TGF-beta action. Moreover, the data suggest that platelet-mediated proliferation of aortic smooth muscle cells in vivo may not result solely from the stimulatory effect of platelet-derived growth factor (PDGF), but rather from an interaction of platelet factors which has the intrinsic ability to limit as well as stimulate mitosis.

Full Text

The Full Text of this article is available as a PDF (813K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Anzano MA, Roberts AB, Meyers CA, Komoriya A, Lamb LC, Smith JM, Sporn MB. Synergistic interaction of two classes of transforming growth factors from murine sarcoma cells. Cancer Res. 1982 Nov;42(11):4776–4778. [PubMed]
  • Assoian RK. Biphasic effects of type beta transforming growth factor on epidermal growth factor receptors in NRK fibroblasts. Functional consequences for epidermal growth factor-stimulated mitosis. J Biol Chem. 1985 Aug 15;260(17):9613–9617. [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]
  • 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]
  • Bowen-Pope DF, Ross R. Is epidermal growth factor present in human blood? Interference with the radioreceptor assay for epidermal growth factor. Biochem Biophys Res Commun. 1983 Aug 12;114(3):1036–1041. [PubMed]
  • Bowen-Pope DF, Vogel A, Ross R. Production of platelet-derived growth factor-like molecules and reduced expression of platelet-derived growth factor receptors accompany transformation by a wide spectrum of agents. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2396–2400. [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. [PubMed]
  • DiCorleto PE, Bowen-Pope DF. Cultured endothelial cells produce a platelet-derived growth factor-like protein. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1919–1923. [PubMed]
  • Doolittle RF, Hunkapiller MW, Hood LE, Devare SG, Robbins KC, Aaronson SA, Antoniades HN. Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science. 1983 Jul 15;221(4607):275–277. [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]
  • Grotendorst GR, Seppä HE, Kleinman HK, Martin GR. Attachment of smooth muscle cells to collagen and their migration toward platelet-derived growth factor. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3669–3672. [PubMed]
  • Heldin CH, Westermark B, Wasteson A. Platelet-derived growth factor: purification and partial characterization. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3722–3726. [PubMed]
  • Kaplan DR, Chao FC, Stiles CD, Antoniades HN, Scher CD. Platelet alpha granules contain a growth factor for fibroblasts. Blood. 1979 Jun;53(6):1043–1052. [PubMed]
  • Kaplan KL, Broekman MJ, Chernoff A, Lesznik GR, Drillings M. Platelet alpha-granule proteins: studies on release and subcellular localization. Blood. 1979 Apr;53(4):604–618. [PubMed]
  • Kaplan KL, Nossel HL, Drillings M, Lesznik G. Radioimmunoassay of platelet factor 4 and beta-thromboglobulin: development and application to studies of platelet release in relation to fibrinopeptide A generation. Br J Haematol. 1978 May;39(1):129–146. [PubMed]
  • Kaplan PL, Ozanne B. Cellular responsiveness to growth factors correlates with a cell's ability to express the transformed phenotype. Cell. 1983 Jul;33(3):931–938. [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]
  • Massagué J. Type beta transforming growth factor from feline sarcoma virus-transformed rat cells. Isolation and biological properties. J Biol Chem. 1984 Aug 10;259(15):9756–9761. [PubMed]
  • Massagué J, Kelly B, Mottola C. Stimulation by insulin-like growth factors is required for cellular transformation by type beta transforming growth factor. J Biol Chem. 1985 Apr 25;260(8):4551–4554. [PubMed]
  • Nilsson J, Sjölund M, Palmberg L, Thyberg J, Heldin CH. Arterial smooth muscle cells in primary culture produce a platelet-derived growth factor-like protein. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4418–4422. [PubMed]
  • Oka Y, Orth DN. Human plasma epidermal growth factor/beta-urogastrone is associated with blood platelets. J Clin Invest. 1983 Jul;72(1):249–259. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Roberts AB, Anzano MA, Wakefield LM, Roche NS, Stern DF, Sporn MB. Type beta transforming growth factor: a bifunctional regulator of cellular growth. Proc Natl Acad Sci U S A. 1985 Jan;82(1):119–123. [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]
  • Roberts AB, Lamb LC, Newton DL, Sporn MB, De Larco JE, Todaro GJ. Transforming growth factors: isolation of polypeptides from virally and chemically transformed cells by acid/ethanol extraction. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3494–3498. [PubMed]
  • Raines EW, Ross R. Platelet-derived growth factor. I. High yield purification and evidence for multiple forms. J Biol Chem. 1982 May 10;257(9):5154–5160. [PubMed]
  • Reidy MA, Schwartz SM. Endothelial regeneration. III. Time course of intimal changes after small defined injury to rat aortic endothelium. Lab Invest. 1981 Apr;44(4):301–308. [PubMed]
  • Ross R. The smooth muscle cell. II. Growth of smooth muscle in culture and formation of elastic fibers. J Cell Biol. 1971 Jul;50(1):172–186. [PMC free article] [PubMed]
  • Ross R, Glomset JA. The pathogenesis of atherosclerosis (first of two parts). N Engl J Med. 1976 Aug 12;295(7):369–377. [PubMed]
  • Ross R, Vogel A. The platelet-derived growth factor. Cell. 1978 Jun;14(2):203–210. [PubMed]
  • Ross R, Glomset J, Kariya B, Harker L. A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1207–1210. [PubMed]
  • Rozengurt E, Stroobant P, Waterfield MD, Deuel TF, Keehan M. Platelet-derived growth factor elicits cyclic AMP accumulation in Swiss 3T3 cells: role of prostaglandin production. Cell. 1983 Aug;34(1):265–272. [PubMed]
  • Savage CR, Jr, Cohen S. Epidermal growth factor and a new derivative. Rapid isolation procedures and biological and chemical characterization. J Biol Chem. 1972 Dec 10;247(23):7609–7611. [PubMed]
  • Seifert RA, Schwartz SM, Bowen-Pope DF. Developmentally regulated production of platelet-derived growth factor-like molecules. Nature. 1984 Oct 18;311(5987):669–671. [PubMed]
  • Senior RM, Griffin GL, Huang JS, Walz DA, Deuel TF. Chemotactic activity of platelet alpha granule proteins for fibroblasts. J Cell Biol. 1983 Feb;96(2):382–385. [PMC free article] [PubMed]
  • Seppä H, Grotendorst G, Seppä S, Schiffmann E, Martin GR. Platelet-derived growth factor in chemotactic for fibroblasts. J Cell Biol. 1982 Feb;92(2):584–588. [PMC free article] [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]
  • Shipley GD, Tucker RF, Moses HL. Type beta transforming growth factor/growth inhibitor stimulates entry of monolayer cultures of AKR-2B cells into S phase after a prolonged prereplicative interval. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4147–4151. [PubMed]
  • Spaet TH, Stemerman MB, Veith FJ, Lejnieks I. Intimal injury and regrowth in the rabbit aorta; medial smooth muscle cells as a source of neointima. Circ Res. 1975 Jan;36(1):58–70. [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]
  • Stiles CD. The molecular biology of platelet-derived growth factor. Cell. 1983 Jul;33(3):653–655. [PubMed]
  • Stroobant P, Waterfield MD. Purification and properties of porcine platelet-derived growth factor. EMBO J. 1984 Dec 1;3(12):2963–2967. [PubMed]
  • Tucker RF, Shipley GD, Moses HL, Holley RW. Growth inhibitor from BSC-1 cells closely related to platelet type beta transforming growth factor. Science. 1984 Nov 9;226(4675):705–707. [PubMed]
  • Tucker RF, Volkenant ME, Branum EL, Moses HL. Comparison of intra- and extracellular transforming growth factors from nontransformed and chemically transformed mouse embryo cells. Cancer Res. 1983 Apr;43(4):1581–1586. [PubMed]
  • Waterfield MD, Scrace GT, Whittle N, Stroobant P, Johnsson A, Wasteson A, Westermark B, Heldin CH, Huang JS, Deuel TF. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature. 1983 Jul 7;304(5921):35–39. [PubMed]
  • Witte LD, Cornicelli JA, Miller RW, Goodman DS. Effect of platelet-derived and endothelial cell-derived growth factors on the low density lipoprotein receptor pathway in cultured human fibroblasts. J Biol Chem. 1982 May 25;257(10):5392–5401. [PubMed]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press