Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Mar;87(6):2177–2181. doi: 10.1073/pnas.87.6.2177

Increased platelet-derived growth factor A-chain expression in human uterine smooth muscle cells during the physiologic hypertrophy of pregnancy.

A E Mendoza 1, R Young 1, S H Orkin 1, T Collins 1
PMCID: PMC53649  PMID: 2315311

Abstract

Platelet-derived growth factor (PDGF) has been implicated in the cell proliferation and directed cell movement in various physiologic and pathologic processes. To explore the role of PDGF in a reversible physiologic process, adaptation of the uterus to pregnancy, expression of PDGF in tissue sections of human gestational myometrium was demonstrated by immunohistochemical techniques and confirmed by nuclease protection analysis. Commensurate with an increase in immunoreactive PDGF expression in the myometrial smooth muscle cells, increased levels of PDGF A-chain mRNA, but not PDGF B-chain or PDGF B-type receptor transcripts, were seen in the gravid uterus relative to the nongravid uterus. The amount of A-chain transcript increased during gestation and diminished during the puerperium. These observations demonstrate PDGF polypeptide expression in situ and implicate PDGF in a normal physiologic process--uterine expansion during pregnancy.

Full text

PDF
2177

Images in this article

2178Image
on p.2178
2179Image
on p.2179
2179Image
on p.2179
2179Image
on p.2179
2179Image
on p.2179
2179Image
on p.2179
2179Image
on p.2179
2179Image
on p.2179
2179Image
on p.2179
2179Image
on p.2179
2180Image
on p.2180
2180Image
on p.2180
2180Image
on p.2180

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baserga R. Growth in size and cell DNA replication. Exp Cell Res. 1984 Mar;151(1):1–5. doi: 10.1007/978-3-642-67986-5_1. [DOI] [PubMed] [Google Scholar]
  2. Benditt E. P. Origins of human atherosclerotic plaques. The role of altered gene expression. Arch Pathol Lab Med. 1988 Oct;112(10):997–1001. [PubMed] [Google Scholar]
  3. Betsholtz C., Johnsson A., Heldin C. H., Westermark B., Lind P., Urdea M. S., Eddy R., Shows T. B., Philpott K., Mellor A. L. 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. doi: 10.1038/320695a0. [DOI] [PubMed] [Google Scholar]
  4. Block L. H., Emmons L. R., 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. doi: 10.1073/pnas.86.7.2388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bonthron D. T., Morton C. C., Orkin S. H., Collins T. Platelet-derived growth factor A chain: gene structure, chromosomal location, and basis for alternative mRNA splicing. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1492–1496. doi: 10.1073/pnas.85.5.1492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bywater M., Rorsman F., Bongcam-Rudloff E., Mark G., Hammacher A., Heldin C. H., Westermark B., Betsholtz C. Expression of recombinant platelet-derived growth factor A- and B-chain homodimers in rat-1 cells and human fibroblasts reveals differences in protein processing and autocrine effects. Mol Cell Biol. 1988 Jul;8(7):2753–2762. doi: 10.1128/mcb.8.7.2753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Castellot J. J., Jr, Addonizio M. L., Rosenberg R., Karnovsky M. J. Cultured endothelial cells produce a heparinlike inhibitor of smooth muscle cell growth. J Cell Biol. 1981 Aug;90(2):372–379. doi: 10.1083/jcb.90.2.372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  9. Chiu I. M., Reddy E. P., Givol D., Robbins K. C., Tronick S. R., Aaronson S. A. Nucleotide sequence analysis identifies the human c-sis proto-oncogene as a structural gene for platelet-derived growth factor. Cell. 1984 May;37(1):123–129. doi: 10.1016/0092-8674(84)90307-6. [DOI] [PubMed] [Google Scholar]
  10. Collins T., Bonthron D. T., Orkin S. H. Alternative RNA splicing affects function of encoded platelet-derived growth factor A chain. Nature. 1987 Aug 13;328(6131):621–624. doi: 10.1038/328621a0. [DOI] [PubMed] [Google Scholar]
  11. Collins T., Ginsburg D., Boss J. M., Orkin S. H., Pober J. S. Cultured human endothelial cells express platelet-derived growth factor B chain: cDNA cloning and structural analysis. Nature. 1985 Aug 22;316(6030):748–750. doi: 10.1038/316748a0. [DOI] [PubMed] [Google Scholar]
  12. Dalla-Favera R., Gallo R. C., Giallongo A., Croce C. M. Chromosomal localization of the human homolog (c-sis) of the simian sarcoma virus onc gene. Science. 1982 Nov 12;218(4573):686–688. doi: 10.1126/science.6291150. [DOI] [PubMed] [Google Scholar]
  13. Deuel T. F., Huang J. S., Huang S. S., Stroobant P., Waterfield M. D. Expression of a platelet-derived growth factor-like protein in simian sarcoma virus transformed cells. Science. 1983 Sep 30;221(4618):1348–1350. doi: 10.1126/science.6310754. [DOI] [PubMed] [Google Scholar]
  14. Deuel T. F., Senior R. M. Growth factors in fibrotic diseases. N Engl J Med. 1987 Jul 23;317(4):236–237. doi: 10.1056/NEJM198707233170409. [DOI] [PubMed] [Google Scholar]
  15. Doolittle R. F., Hunkapiller M. W., Hood L. E., Devare S. G., Robbins K. C., Aaronson S. A., Antoniades H. N. 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. doi: 10.1126/science.6304883. [DOI] [PubMed] [Google Scholar]
  16. Geisterfer A. A., Peach M. J., Owens G. K. Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ Res. 1988 Apr;62(4):749–756. doi: 10.1161/01.res.62.4.749. [DOI] [PubMed] [Google Scholar]
  17. Gordon D., Schwartz S. M., Benditt E. P., Wilcox J. N. Growth factors and cell proliferation in human atherosclerosis. Transplant Proc. 1989 Aug;21(4):3692–3694. [PubMed] [Google Scholar]
  18. Goustin A. S., Betsholtz C., Pfeifer-Ohlsson S., Persson H., Rydnert J., Bywater M., Holmgren G., Heldin C. H., Westermark B., Ohlsson R. Coexpression of the sis and myc proto-oncogenes in developing human placenta suggests autocrine control of trophoblast growth. Cell. 1985 May;41(1):301–312. doi: 10.1016/0092-8674(85)90083-2. [DOI] [PubMed] [Google Scholar]
  19. Gronwald R. G., Grant F. J., Haldeman B. A., Hart C. E., O'Hara P. J., Hagen F. S., Ross R., Bowen-Pope D. F., Murray M. J. 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. doi: 10.1073/pnas.85.10.3435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Grotendorst G. R., Chang T., Seppä H. E., Kleinman H. K., Martin G. R. Platelet-derived growth factor is a chemoattractant for vascular smooth muscle cells. J Cell Physiol. 1982 Nov;113(2):261–266. doi: 10.1002/jcp.1041130213. [DOI] [PubMed] [Google Scholar]
  21. Hammacher A., Hellman U., Johnsson A., Ostman A., Gunnarsson K., Westermark B., Wasteson A., Heldin C. H. A major part of platelet-derived growth factor purified from human platelets is a heterodimer of one A and one B chain. J Biol Chem. 1988 Nov 5;263(31):16493–16498. [PubMed] [Google Scholar]
  22. Heldin C. H., Johnsson A., Wennergren S., Wernstedt C., Betsholtz C., Westermark B. A human osteosarcoma cell line secretes a growth factor structurally related to a homodimer of PDGF A-chains. Nature. 1986 Feb 6;319(6053):511–514. doi: 10.1038/319511a0. [DOI] [PubMed] [Google Scholar]
  23. Johnsson A., Heldin C. H., Wasteson A., Westermark B., Deuel T. F., Huang J. S., Seeburg P. H., Gray A., Ullrich A., Scrace G. The c-sis gene encodes a precursor of the B chain of platelet-derived growth factor. EMBO J. 1984 May;3(5):921–928. doi: 10.1002/j.1460-2075.1984.tb01908.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Josephs S. F., Guo C., Ratner L., Wong-Staal F. Human-proto-oncogene nucleotide sequences corresponding to the transforming region of simian sarcoma virus. Science. 1984 Feb 3;223(4635):487–491. doi: 10.1126/science.6318322. [DOI] [PubMed] [Google Scholar]
  25. Kohler N., Lipton A. Platelets as a source of fibroblast growth-promoting activity. Exp Cell Res. 1974 Aug;87(2):297–301. doi: 10.1016/0014-4827(74)90484-4. [DOI] [PubMed] [Google Scholar]
  26. Libby P., Warner S. J., Friedman G. B. Interleukin 1: a mitogen for human vascular smooth muscle cells that induces the release of growth-inhibitory prostanoids. J Clin Invest. 1988 Feb;81(2):487–498. doi: 10.1172/JCI113346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Libby P., Warner S. J., Salomon R. N., Birinyi L. K. Production of platelet-derived growth factor-like mitogen by smooth-muscle cells from human atheroma. N Engl J Med. 1988 Jun 9;318(23):1493–1498. doi: 10.1056/NEJM198806093182303. [DOI] [PubMed] [Google Scholar]
  28. Majesky M. W., Daemen M. J., Schwartz S. M. 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] [Google Scholar]
  29. Matsui T., Heidaran M., Miki T., Popescu N., La Rochelle W., Kraus M., Pierce J., Aaronson S. Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes. Science. 1989 Feb 10;243(4892):800–804. doi: 10.1126/science.2536956. [DOI] [PubMed] [Google Scholar]
  30. Mercola M., Stiles C. D. Growth factor superfamilies and mammalian embryogenesis. Development. 1988 Mar;102(3):451–460. doi: 10.1242/dev.102.3.451. [DOI] [PubMed] [Google Scholar]
  31. Naftilan A. J., Pratt R. E., Dzau V. J. Induction of platelet-derived growth factor A-chain and c-myc gene expressions by angiotensin II in cultured rat vascular smooth muscle cells. J Clin Invest. 1989 Apr;83(4):1419–1424. doi: 10.1172/JCI114032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Owens G. K., Geisterfer A. A., Yang Y. W., Komoriya A. Transforming growth factor-beta-induced growth inhibition and cellular hypertrophy in cultured vascular smooth muscle cells. J Cell Biol. 1988 Aug;107(2):771–780. doi: 10.1083/jcb.107.2.771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rao C. D., Igarashi H., Chiu I. M., Robbins K. C., Aaronson S. A. Structure and sequence of the human c-sis/platelet-derived growth factor 2 (SIS/PDGF2) transcriptional unit. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2392–2396. doi: 10.1073/pnas.83.8.2392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rao C. D., Pech M., Robbins K. C., Aaronson S. A. The 5' untranslated sequence of the c-sis/platelet-derived growth factor 2 transcript is a potent translational inhibitor. Mol Cell Biol. 1988 Jan;8(1):284–292. doi: 10.1128/mcb.8.1.284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ratner L., Thielan B., Collins T. Sequences of the 5' portion of the human c-sis gene: characterization of the transcriptional promoter and regulation of expression of the protein product by 5' untranslated mRNA sequences. Nucleic Acids Res. 1987 Aug 11;15(15):6017–6036. doi: 10.1093/nar/15.15.6017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Robbins K. C., Antoniades H. N., Devare S. G., Hunkapiller M. W., Aaronson S. A. Structural and immunological similarities between simian sarcoma virus gene product(s) and human platelet-derived growth factor. Nature. 1983 Oct 13;305(5935):605–608. doi: 10.1038/305605a0. [DOI] [PubMed] [Google Scholar]
  37. 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. doi: 10.1073/pnas.71.4.1207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Ross R., Raines E. W., Bowen-Pope D. F. The biology of platelet-derived growth factor. Cell. 1986 Jul 18;46(2):155–169. doi: 10.1016/0092-8674(86)90733-6. [DOI] [PubMed] [Google Scholar]
  39. Seifert R. A., Schwartz S. M., Bowen-Pope D. F. Developmentally regulated production of platelet-derived growth factor-like molecules. Nature. 1984 Oct 18;311(5987):669–671. doi: 10.1038/311669a0. [DOI] [PubMed] [Google Scholar]
  40. Shaw K. J., Do Y. S., Kjos S., Anderson P. W., Shinagawa T., Dubeau L., Hsueh W. A. Human decidua is a major source of renin. J Clin Invest. 1989 Jun;83(6):2085–2092. doi: 10.1172/JCI114121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Walker L. N., Bowen-Pope D. F., Ross R., Reidy M. A. 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. doi: 10.1073/pnas.83.19.7311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Waterfield M. D., Scrace G. T., Whittle N., Stroobant P., Johnsson A., Wasteson A., Westermark B., Heldin C. H., Huang J. S., Deuel T. F. 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. doi: 10.1038/304035a0. [DOI] [PubMed] [Google Scholar]
  43. Wise R. J., Orkin S. H., Collins T. Aberrant expression of platelet-derived growth factor A-chain cDNAs due to cryptic splicing of RNA transcripts in COS-1 cells. Nucleic Acids Res. 1989 Aug 25;17(16):6591–6601. doi: 10.1093/nar/17.16.6591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wise R. J., Pittman D. D., Handin R. I., Kaufman R. J., Orkin S. H. The propeptide of von Willebrand factor independently mediates the assembly of von Willebrand multimers. Cell. 1988 Jan 29;52(2):229–236. doi: 10.1016/0092-8674(88)90511-9. [DOI] [PubMed] [Google Scholar]

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

RESOURCES