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. 1992 May;89(5):1629–1635. doi: 10.1172/JCI115759

Transforming growth factor-beta 1 is decreased in remodeling hypertensive bovine pulmonary arteries.

M D Botney 1, W C Parks 1, E C Crouch 1, K Stenmark 1, R P Mecham 1
PMCID: PMC443039  PMID: 1569202

Abstract

The development of pulmonary hypertension in hypoxic newborn calves is associated with a complex pattern of increased tropoelastin and type I procollagen synthesis and deposition by smooth muscle cells in large elastic pulmonary arteries compared to normoxic controls. We examined the possibility that transforming growth factor-beta 1 (TGF-beta 1) may be associated with the production of extracellular matrix protein in this model of pulmonary hypertension. Medial smooth muscle cells in both normotensive and hypertensive vessels, as assessed by immunohistochemistry, were the major source of TGF-beta 1. Staining was confined to foci of smooth muscle cells in the outer media and appeared greater in normotensive than hypertensive vessels. Consistent with the immunohistochemistry, a progressive, age-dependent increase in normotensive pulmonary artery TGF-beta 1 mRNA was observed after birth, whereas TGF-beta 1 mRNA remained at low, basal levels in hypertensive, remodeling pulmonary arteries. These observations suggest that local expression of TGF-beta 1 is not associated with increased extracellular matrix protein synthesis in this model of hypoxic pulmonary hypertension.

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Selected References

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

  1. Allen K., Haworth S. G. Human postnatal pulmonary arterial remodeling. Ultrastructural studies of smooth muscle cell and connective tissue maturation. Lab Invest. 1988 Nov;59(5):702–709. [PubMed] [Google Scholar]
  2. Arcari P., Martinelli R., Salvatore F. The complete sequence of a full length cDNA for human liver glyceraldehyde-3-phosphate dehydrogenase: evidence for multiple mRNA species. Nucleic Acids Res. 1984 Dec 11;12(23):9179–9189. doi: 10.1093/nar/12.23.9179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen J. K., Hoshi H., McKeehan W. L. Transforming growth factor type beta specifically stimulates synthesis of proteoglycan in human adult arterial smooth muscle cells. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5287–5291. doi: 10.1073/pnas.84.15.5287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Czaja M. J., Weiner F. R., Flanders K. C., Giambrone M. A., Wind R., Biempica L., Zern M. A. In vitro and in vivo association of transforming growth factor-beta 1 with hepatic fibrosis. J Cell Biol. 1989 Jun;108(6):2477–2482. doi: 10.1083/jcb.108.6.2477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Derynck R., Jarrett J. A., Chen E. Y., Eaton D. H., Bell J. R., Assoian R. K., Roberts A. B., Sporn M. B., Goeddel D. V. Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells. Nature. 1985 Aug 22;316(6030):701–705. doi: 10.1038/316701a0. [DOI] [PubMed] [Google Scholar]
  6. Fine A., Goldstein R. H. The effect of transforming growth factor-beta on cell proliferation and collagen formation by lung fibroblasts. J Biol Chem. 1987 Mar 15;262(8):3897–3902. [PubMed] [Google Scholar]
  7. Fine A., Poliks C. F., Donahue L. P., Smith B. D., Goldstein R. H. The differential effect of prostaglandin E2 on transforming growth factor-beta and insulin-induced collagen formation in lung fibroblasts. J Biol Chem. 1989 Oct 15;264(29):16988–16991. [PubMed] [Google Scholar]
  8. Flanders K. C., Thompson N. L., Cissel D. S., Van Obberghen-Schilling E., Baker C. C., Kass M. E., Ellingsworth L. R., Roberts A. B., Sporn M. B. Transforming growth factor-beta 1: histochemical localization with antibodies to different epitopes. J Cell Biol. 1989 Feb;108(2):653–660. doi: 10.1083/jcb.108.2.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hall S. M., Haworth S. G. Conducting pulmonary arteries: structural adaptation to extrauterine life in the pig. Cardiovasc Res. 1987 Mar;21(3):208–216. doi: 10.1093/cvr/21.3.208. [DOI] [PubMed] [Google Scholar]
  10. Ignotz R. A., Endo T., Massagué J. Regulation of fibronectin and type I collagen mRNA levels by transforming growth factor-beta. J Biol Chem. 1987 May 15;262(14):6443–6446. [PubMed] [Google Scholar]
  11. Ignotz R. A., 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] [Google Scholar]
  12. Jakowlew S. B., Dillard P. J., Sporn M. B., Roberts A. B. Complementary deoxyribonucleic acid cloning of a messenger ribonucleic acid encoding transforming growth factor beta 4 from chicken embryo chondrocytes. Mol Endocrinol. 1988 Dec;2(12):1186–1195. doi: 10.1210/mend-2-12-1186. [DOI] [PubMed] [Google Scholar]
  13. Khalil N., Bereznay O., Sporn M., Greenberg A. H. Macrophage production of transforming growth factor beta and fibroblast collagen synthesis in chronic pulmonary inflammation. J Exp Med. 1989 Sep 1;170(3):727–737. doi: 10.1084/jem.170.3.727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kondaiah P., Sands M. J., Smith J. M., Fields A., Roberts A. B., Sporn M. B., Melton D. A. Identification of a novel transforming growth factor-beta (TGF-beta 5) mRNA in Xenopus laevis. J Biol Chem. 1990 Jan 15;265(2):1089–1093. [PubMed] [Google Scholar]
  15. Kourembanas S., Hannan R. L., Faller D. V. Oxygen tension regulates the expression of the platelet-derived growth factor-B chain gene in human endothelial cells. J Clin Invest. 1990 Aug;86(2):670–674. doi: 10.1172/JCI114759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Larzul D., Guigue F., Sninsky J. J., Mack D. H., Bréchot C., Guesdon J. L. Detection of hepatitis B virus sequences in serum by using in vitro enzymatic amplification. J Virol Methods. 1988 Jul;20(3):227–237. doi: 10.1016/0166-0934(88)90126-7. [DOI] [PubMed] [Google Scholar]
  17. Liau G., Chan L. M. Regulation of extracellular matrix RNA levels in cultured smooth muscle cells. Relationship to cellular quiescence. J Biol Chem. 1989 Jun 15;264(17):10315–10320. [PubMed] [Google Scholar]
  18. Liu J. M., Davidson J. M. The elastogenic effect of recombinant transforming growth factor-beta on porcine aortic smooth muscle cells. Biochem Biophys Res Commun. 1988 Aug 15;154(3):895–901. doi: 10.1016/0006-291x(88)90224-0. [DOI] [PubMed] [Google Scholar]
  19. Majesky M. W., Lindner V., Twardzik D. R., Schwartz S. M., Reidy M. A. Production of transforming growth factor beta 1 during repair of arterial injury. J Clin Invest. 1991 Sep;88(3):904–910. doi: 10.1172/JCI115393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Majesky M. W., Schwartz S. M., Clowes M. M., Clowes A. W. Heparin regulates smooth muscle S phase entry in the injured rat carotid artery. Circ Res. 1987 Aug;61(2):296–300. doi: 10.1161/01.res.61.2.296. [DOI] [PubMed] [Google Scholar]
  21. Massagué J. The TGF-beta family of growth and differentiation factors. Cell. 1987 May 22;49(4):437–438. doi: 10.1016/0092-8674(87)90443-0. [DOI] [PubMed] [Google Scholar]
  22. McGowan S. E., McNamer R. Transforming growth factor-beta increases elastin production by neonatal rat lung fibroblasts. Am J Respir Cell Mol Biol. 1990 Oct;3(4):369–376. doi: 10.1165/ajrcmb/3.4.369. [DOI] [PubMed] [Google Scholar]
  23. Mecham R. P., Whitehouse L. A., Wrenn D. S., Parks W. C., Griffin G. L., Senior R. M., Crouch E. C., Stenmark K. R., Voelkel N. F. Smooth muscle-mediated connective tissue remodeling in pulmonary hypertension. Science. 1987 Jul 24;237(4813):423–426. doi: 10.1126/science.3603030. [DOI] [PubMed] [Google Scholar]
  24. Meyrick B., Reid L. Hypoxia-induced structural changes in the media and adventitia of the rat hilar pulmonary artery and their regression. Am J Pathol. 1980 Jul;100(1):151–178. [PMC free article] [PubMed] [Google Scholar]
  25. Parks W. C., Secrist H., Wu L. C., Mecham R. P. Developmental regulation of tropoelastin isoforms. J Biol Chem. 1988 Mar 25;263(9):4416–4423. [PubMed] [Google Scholar]
  26. Peltonen J., Kähäri L., Jaakkola S., Kähäri V. M., Varga J., Uitto J., Jimenez S. A. Evaluation of transforming growth factor beta and type I procollagen gene expression in fibrotic skin diseases by in situ hybridization. J Invest Dermatol. 1990 Mar;94(3):365–371. doi: 10.1111/1523-1747.ep12874491. [DOI] [PubMed] [Google Scholar]
  27. Penttinen R. P., Kobayashi S., Bornstein P. Transforming growth factor beta increases mRNA for matrix proteins both in the presence and in the absence of changes in mRNA stability. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1105–1108. doi: 10.1073/pnas.85.4.1105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Perkett E. A., Lyons R. M., Moses H. L., Brigham K. L., Meyrick B. Transforming growth factor-beta activity in sheep lung lymph during the development of pulmonary hypertension. J Clin Invest. 1990 Nov;86(5):1459–1464. doi: 10.1172/JCI114862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Poiani G. J., Tozzi C. A., Yohn S. E., Pierce R. A., Belsky S. A., Berg R. A., Yu S. Y., Deak S. B., Riley D. J. Collagen and elastin metabolism in hypertensive pulmonary arteries of rats. Circ Res. 1990 Apr;66(4):968–978. doi: 10.1161/01.res.66.4.968. [DOI] [PubMed] [Google Scholar]
  30. Prosser I. W., Stenmark K. R., Suthar M., Crouch E. C., Mecham R. P., Parks W. C. Regional heterogeneity of elastin and collagen gene expression in intralobar arteries in response to hypoxic pulmonary hypertension as demonstrated by in situ hybridization. Am J Pathol. 1989 Dec;135(6):1073–1088. [PMC free article] [PubMed] [Google Scholar]
  31. Raghow B., Irish P., Kang A. H. 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. doi: 10.1172/JCI114369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Roberts A. B., Anzano M. A., Wakefield L. M., Roche N. S., Stern D. F., Sporn M. B. Type beta transforming growth factor: a bifunctional regulator of cellular growth. Proc Natl Acad Sci U S A. 1985 Jan;82(1):119–123. doi: 10.1073/pnas.82.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Roberts A. B., Sporn M. B., Assoian R. K., Smith J. M., Roche N. S., Wakefield L. M., Heine U. I., Liotta L. A., Falanga V., Kehrl J. H. 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. doi: 10.1073/pnas.83.12.4167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sabath D. E., Broome H. E., Prystowsky M. B. Glyceraldehyde-3-phosphate dehydrogenase mRNA is a major interleukin 2-induced transcript in a cloned T-helper lymphocyte. Gene. 1990 Jul 16;91(2):185–191. doi: 10.1016/0378-1119(90)90087-8. [DOI] [PubMed] [Google Scholar]
  35. Sarzani R., Brecher P., Chobanian A. V. Growth factor expression in aorta of normotensive and hypertensive rats. J Clin Invest. 1989 Apr;83(4):1404–1408. doi: 10.1172/JCI114029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sporn M. B., Roberts A. B., Wakefield L. M., Assoian R. K. Transforming growth factor-beta: biological function and chemical structure. Science. 1986 Aug 1;233(4763):532–534. doi: 10.1126/science.3487831. [DOI] [PubMed] [Google Scholar]
  37. Stenmark K. R., Fasules J., Hyde D. M., Voelkel N. F., Henson J., Tucker A., Wilson H., Reeves J. T. Severe pulmonary hypertension and arterial adventitial changes in newborn calves at 4,300 m. J Appl Physiol (1985) 1987 Feb;62(2):821–830. doi: 10.1152/jappl.1987.62.2.821. [DOI] [PubMed] [Google Scholar]
  38. Wrenn D. S., Parks W. C., Whitehouse L. A., Crouch E. C., Kucich U., Rosenbloom J., Mecham R. P. Identification of multiple tropoelastins secreted by bovine cells. J Biol Chem. 1987 Feb 15;262(5):2244–2249. [PubMed] [Google Scholar]
  39. ten Dijke P., Hansen P., Iwata K. K., Pieler C., Foulkes J. G. Identification of another member of the transforming growth factor type beta gene family. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4715–4719. doi: 10.1073/pnas.85.13.4715. [DOI] [PMC free article] [PubMed] [Google Scholar]

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