Logo of jcellbiolHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Cell Biol. 1990 Nov 1; 111(5): 2149–2158.
PMCID: PMC2116329

PDGF ligand and receptor gene expression during repair of arterial injury


Smooth muscle cells (SMC) in rat carotid artery leave the quiescent state and proliferate after balloon catheter injury, but the signals for mitogenesis are not known. In this study, the possibility that cells within damaged arteries produce a growth factor that could act locally to stimulate SMC replication and repair was examined. We found that the genes for PDGF-A and -B (ligand) and PDGF receptor (alpha and beta subunits) were expressed in normal and injured carotid arteries and were independently regulated during repair of carotid injury. Two phases of PDGF ligand and receptor gene expression were observed: (a) In the early stage, a large decrease in PDGF beta-receptor mRNA levels preceded 10- to 12-fold increases in PDGF-A transcript abundance in the first 6 h after wounding. No change in PDGF alpha-receptor or PDGF-B gene expression was found at these times. (b) In the chronic phase, 2 wk after injury, neointimal tissue had lower levels of PDGF alpha- receptor mRNA (threefold) and higher levels of PDGF beta-receptor mRNA (three- to fivefold) than did restored media. Moreover, in situ hybridization studies identified a subpopulation of neointimal SMC localized at or near the luminal surface with a different pattern of gene expression than the underlying carotid SMC. Luminal SMC were strongly positive for PDGF-A and PDGF beta-receptor transcripts, while showing little or no hybridization for PDGF-B or PDGF alpha-receptor. Immunohistochemical studies showed strongly positive staining for PDGF- A in SMC along the luminal surface. These data show that changes in PDGF ligand and receptor expression occur at specific times and locations in injured carotid artery and suggest that these changes may play a role in regulating arterial wound repair.

Full Text

The Full Text of this article is available as a PDF (5.2M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Barrett TB, Benditt EP. Platelet-derived growth factor gene expression in human atherosclerotic plaques and normal artery wall. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2810–2814. [PMC free article] [PubMed]
  • Barrett TB, Gajdusek CM, Schwartz SM, McDougall JK, Benditt EP. Expression of the sis gene by endothelial cells in culture and in vivo. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6772–6774. [PMC free article] [PubMed]
  • Berk BC, Alexander RW, Brock TA, Gimbrone MA, Jr, Webb RC. Vasoconstriction: a new activity for platelet-derived growth factor. Science. 1986 Apr 4;232(4746):87–90. [PubMed]
  • Betsholtz C, Johnsson A, Heldin CH, Westermark B, Lind P, Urdea MS, Eddy R, Shows TB, Philpott K, Mellor AL, et al. cDNA sequence and chromosomal localization of human platelet-derived growth factor A-chain and its expression in tumour cell lines. Nature. 1986 Apr 24;320(6064):695–699. [PubMed]
  • Björkerud S, Bondjers G. Arterial repair and atherosclerosis after mechanical injury. 2. Tissue response after induction of a total local necrosis deep longitudinal injury. Atherosclerosis. 1971 Sep-Oct;14(2):259–276. [PubMed]
  • Block LH, Emmons LR, Vogt E, Sachinidis A, Vetter W, Hoppe J. Ca2+-channel blockers inhibit the action of recombinant platelet-derived growth factor in vascular smooth muscle cells. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2388–2392. [PMC free article] [PubMed]
  • Bowen-Pope DF, Hart CE, Seifert RA. Sera and conditioned media contain different isoforms of platelet-derived growth factor (PDGF) which bind to different classes of PDGF receptor. J Biol Chem. 1989 Feb 15;264(5):2502–2508. [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Claesson-Welsh L, Eriksson A, Morén A, Severinsson L, Ek B, Ostman A, Betsholtz C, Heldin CH. cDNA cloning and expression of a human platelet-derived growth factor (PDGF) receptor specific for B-chain-containing PDGF molecules. Mol Cell Biol. 1988 Aug;8(8):3476–3486. [PMC free article] [PubMed]
  • Clemmons DR, Van Wyk JJ. Evidence for a functional role of endogenously produced somatomedinlike peptides in the regulation of DNA synthesis in cultured human fibroblasts and porcine smooth muscle cells. J Clin Invest. 1985 Jun;75(6):1914–1918. [PMC free article] [PubMed]
  • Clowes AW, Schwartz SM. Significance of quiescent smooth muscle migration in the injured rat carotid artery. Circ Res. 1985 Jan;56(1):139–145. [PubMed]
  • Clowes AW, Reidy MA, Clowes MM. Kinetics of cellular proliferation after arterial injury. I. Smooth muscle growth in the absence of endothelium. Lab Invest. 1983 Sep;49(3):327–333. [PubMed]
  • Clowes AW, Clowes MM, Reidy MA. Kinetics of cellular proliferation after arterial injury. III. Endothelial and smooth muscle growth in chronically denuded vessels. Lab Invest. 1986 Mar;54(3):295–303. [PubMed]
  • Cochran BH, Lillquist JS, Stiles CD. Post-transcriptional control of protein synthesis in Balb/c-3T3 cells by platelet-derived growth factor and platelet-poor plasma. J Cell Physiol. 1981 Dec;109(3):429–438. [PubMed]
  • Collins T, Ginsburg D, Boss JM, Orkin SH, Pober JS. Cultured human endothelial cells express platelet-derived growth factor B chain: cDNA cloning and structural analysis. Nature. 1985 Aug 22;316(6030):748–750. [PubMed]
  • Curran T, Peters G, Van Beveren C, Teich NM, Verma IM. FBJ murine osteosarcoma virus: identification and molecular cloning of biologically active proviral DNA. J Virol. 1982 Nov;44(2):674–682. [PMC free article] [PubMed]
  • Davies PF, Olesen SP, Clapham DE, Morrel EM, Schoen FJ. Endothelial communication. State of the art lecture. Hypertension. 1988 Jun;11(6 Pt 2):563–572. [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. [PMC free article] [PubMed]
  • Fingerle J, Johnson R, Clowes AW, Majesky MW, Reidy MA. Role of platelets in smooth muscle cell proliferation and migration after vascular injury in rat carotid artery. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8412–8416. [PMC free article] [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. [PMC free article] [PubMed]
  • Gronwald RG, Grant FJ, Haldeman BA, Hart CE, O'Hara PJ, Hagen FS, Ross R, Bowen-Pope DF, Murray MJ. Cloning and expression of a cDNA coding for the human platelet-derived growth factor receptor: evidence for more than one receptor class. Proc Natl Acad Sci U S A. 1988 May;85(10):3435–3439. [PMC free article] [PubMed]
  • Gronwald RG, Seifert RA, Bowen-Pope DF. Differential regulation of expression of two platelet-derived growth factor receptor subunits by transforming growth factor-beta. J Biol Chem. 1989 May 15;264(14):8120–8125. [PubMed]
  • Groves HM, Kinlough-Rathbone RL, Richardson M, Moore S, Mustard JF. Platelet interaction with damaged rabbit aorta. Lab Invest. 1979 Feb;40(2):194–200. [PubMed]
  • Grünwald J, Haudenschild CC. Intimal injury in vivo activates vascular smooth muscle cell migration and explant outgrowth in vitro. Arteriosclerosis. 1984 May-Jun;4(3):183–188. [PubMed]
  • Hart CE, Forstrom JW, Kelly JD, Seifert RA, Smith RA, Ross R, Murray MJ, Bowen-Pope DF. Two classes of PDGF receptor recognize different isoforms of PDGF. Science. 1988 Jun 10;240(4858):1529–1531. [PubMed]
  • Hart CE, Bailey M, Curtis DA, Osborn S, Raines E, Ross R, Forstrom JW. Purification of PDGF-AB and PDGF-BB from human platelet extracts and identification of all three PDGF dimers in human platelets. Biochemistry. 1990 Jan 9;29(1):166–172. [PubMed]
  • Heldin CH, Bäckström G, Ostman A, Hammacher A, Rönnstrand L, Rubin K, Nistér M, Westermark B. Binding of different dimeric forms of PDGF to human fibroblasts: evidence for two separate receptor types. EMBO J. 1988 May;7(5):1387–1393. [PMC free article] [PubMed]
  • Heldin CH, Ernlund A, Rorsman C, Rönnstrand L. Dimerization of B-type platelet-derived growth factor receptors occurs after ligand binding and is closely associated with receptor kinase activation. J Biol Chem. 1989 May 25;264(15):8905–8912. [PubMed]
  • Jørgensen L, Grøthe AG, Groves HM, Kinlough-Rathbone RL, Richardson M, Mustard JF. Sequence of cellular responses in rabbit aortas following one and two injuries with a balloon catheter. Br J Exp Pathol. 1988 Aug;69(4):473–486. [PMC free article] [PubMed]
  • Jonasson L, Holm J, Hansson GK. Smooth muscle cells express Ia antigens during arterial response to injury. Lab Invest. 1988 Mar;58(3):310–315. [PubMed]
  • Kazlauskas A, Bowen-Pope D, Seifert R, Hart CE, Cooper JA. Different effects of homo- and heterodimers of platelet-derived growth factor A and B chains on human and mouse fibroblasts. EMBO J. 1988 Dec 1;7(12):3727–3735. [PMC free article] [PubMed]
  • Lee KH, Bowen-Pope DF, Reed RR. Isolation and characterization of the alpha platelet-derived growth factor receptor from rat olfactory epithelium. Mol Cell Biol. 1990 May;10(5):2237–2246. [PMC free article] [PubMed]
  • Libby P, Salomon RN, Payne DD, Schoen FJ, Pober JS. Functions of vascular wall cells related to development of transplantation-associated coronary arteriosclerosis. Transplant Proc. 1989 Aug;21(4):3677–3684. [PubMed]
  • Majack RA, Majesky MW, Goodman LV. Role of PDGF-A expression in the control of vascular smooth muscle cell growth by transforming growth factor-beta. J Cell Biol. 1990 Jul;111(1):239–247. [PMC free article] [PubMed]
  • Majesky MW, Benditt EP, Schwartz SM. Expression and developmental control of platelet-derived growth factor A-chain and B-chain/Sis genes in rat aortic smooth muscle cells. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1524–1528. [PMC free article] [PubMed]
  • Majesky MW, Daemen MJ, Schwartz SM. Alpha 1-adrenergic stimulation of platelet-derived growth factor A-chain gene expression in rat aorta. J Biol Chem. 1990 Jan 15;265(2):1082–1088. [PubMed]
  • Majesky MW, Schwartz SM, Clowes MM, Clowes AW. Heparin regulates smooth muscle S phase entry in the injured rat carotid artery. Circ Res. 1987 Aug;61(2):296–300. [PubMed]
  • Nistér M, Hammacher A, Mellström K, Siegbahn A, Rönnstrand L, Westermark B, Heldin CH. A glioma-derived PDGF A chain homodimer has different functional activities from a PDGF AB heterodimer purified from human platelets. Cell. 1988 Mar 25;52(6):791–799. [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. [PMC free article] [PubMed]
  • Paulsson Y, Hammacher A, Heldin CH, Westermark B. Possible positive autocrine feedback in the prereplicative phase of human fibroblasts. Nature. 1987 Aug 20;328(6132):715–717. [PubMed]
  • Pegg AE. Recent advances in the biochemistry of polyamines in eukaryotes. Biochem J. 1986 Mar 1;234(2):249–262. [PMC free article] [PubMed]
  • Raines EW, Dower SK, Ross R. Interleukin-1 mitogenic activity for fibroblasts and smooth muscle cells is due to PDGF-AA. Science. 1989 Jan 20;243(4889):393–396. [PubMed]
  • Ratner L, Josephs SF, Jarrett R, Reitz MS, Jr, Wong-Staal F. Nucleotide sequence of transforming human c-sis cDNA clones with homology to platelet-derived growth factor. Nucleic Acids Res. 1985 Jul 25;13(14):5007–5018. [PMC free article] [PubMed]
  • Reidy MA. A reassessment of endothelial injury and arterial lesion formation. Lab Invest. 1985 Nov;53(5):513–520. [PubMed]
  • Rhee CY, Herz F, Spaet TH. Accelerated culture of aortic smooth muscle cells. Thromb Res. 1977 Jul;11(1):90–94. [PubMed]
  • Ross R. The pathogenesis of atherosclerosis--an update. N Engl J Med. 1986 Feb 20;314(8):488–500. [PubMed]
  • Ross R, Raines EW, Bowen-Pope DF. The biology of platelet-derived growth factor. Cell. 1986 Jul 18;46(2):155–169. [PubMed]
  • Rubin K, Tingström A, Hansson GK, Larsson E, Rönnstrand L, Klareskog L, Claesson-Welsh L, Heldin CH, Fellström B, Terracio L. Induction of B-type receptors for platelet-derived growth factor in vascular inflammation: possible implications for development of vascular proliferative lesions. Lancet. 1988 Jun 18;1(8599):1353–1356. [PubMed]
  • Sadler JE, Shelton-Inloes BB, Sorace JM, Harlan JM, Titani K, Davie EW. Cloning and characterization of two cDNAs coding for human von Willebrand factor. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6394–6398. [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]
  • Schwartz SM, Stemerman MB, Benditt EP. The aortic intima. II. Repair of the aortic lining after mechanical denudation. Am J Pathol. 1975 Oct;81(1):15–42. [PMC free article] [PubMed]
  • Schwartz SM, Reidy MR, Clowes A. Kinetics of atherosclerosis: a stem cell model. Ann N Y Acad Sci. 1985;454:292–304. [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]
  • Seifert RA, Hart CE, Phillips PE, Forstrom JW, Ross R, Murray MJ, Bowen-Pope DF. Two different subunits associate to create isoform-specific platelet-derived growth factor receptors. J Biol Chem. 1989 May 25;264(15):8771–8778. [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]
  • 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]
  • Stemerman MB, Ross R. Experimental arteriosclerosis. I. Fibrous plaque formation in primates, an electron microscope study. J Exp Med. 1972 Oct 1;136(4):769–789. [PMC free article] [PubMed]
  • Stimac E, Groppi VE, Jr, Coffino P. Inhibition of protein synthesis stabilizes histone mRNA. Mol Cell Biol. 1984 Oct;4(10):2082–2090. [PMC free article] [PubMed]
  • Terracio L, Rönnstrand L, Tingström A, Rubin K, Claesson-Welsh L, Funa K, Heldin CH. Induction of platelet-derived growth factor receptor expression in smooth muscle cells and fibroblasts upon tissue culturing. J Cell Biol. 1988 Nov;107(5):1947–1957. [PMC free article] [PubMed]
  • Walker LN, Bowen-Pope DF, Ross R, Reidy MA. Production of platelet-derived growth factor-like molecules by cultured arterial smooth muscle cells accompanies proliferation after arterial injury. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7311–7315. [PMC free article] [PubMed]
  • Wilcox JN, Smith KM, Williams LT, Schwartz SM, Gordon D. Platelet-derived growth factor mRNA detection in human atherosclerotic plaques by in situ hybridization. J Clin Invest. 1988 Sep;82(3):1134–1143. [PMC free article] [PubMed]
  • Williams LT. Signal transduction by the platelet-derived growth factor receptor. Science. 1989 Mar 24;243(4898):1564–1570. [PubMed]
  • Yarden Y, Escobedo JA, Kuang WJ, Yang-Feng TL, Daniel TO, Tremble PM, Chen EY, Ando ME, Harkins RN, Francke U, et al. Structure of the receptor for platelet-derived growth factor helps define a family of closely related growth factor receptors. Nature. 1986 Sep 18;323(6085):226–232. [PubMed]
  • Zerwes HG, Risau W. Polarized secretion of a platelet-derived growth factor-like chemotactic factor by endothelial cells in vitro. J Cell Biol. 1987 Nov;105(5):2037–2041. [PMC free article] [PubMed]

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


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...