Platelet-derived growth factor is a cofactor in the induction of 1α(I) procollagen expression by transforming growth factor-β1 in smooth muscle cells

B. G. Halloran, B. J. So, B. T. Baxter, G. A. Sicard, D. Brenin

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Abstract

Purpose: Depending on the derivation of vascular smooth muscle cells (SMC), transforming growth factor-β1 (TGF-β1) has variable effects on proliferation and expression of extracellular matrix. Relatively little is known about TGF-β1's effects on human arterial SMC. Therefore, we sought to determine the effects of TGF-β1 on human arterial SMC proliferation and 1α(I) procollagen expression. The mechanisms by which TGF-β1 regulate type I procollagen expression were also investigated. Methods: SMC cultures were established from the aorta of transplant donors. Serial doses of TGF-β1 were applied, and cellular proliferation assessed by cell counting and tritiated thymidine incorporation. Total cellular ribonucleic acid (RNA) was analyzed by reverse transcription-polymerase chain reaction and Northern blot for changes in 1α(I) procollagen and platelet-derived growth factor (PDGF)-A transcripts. Results: In a dose-dependent manner, TGF-β1 inhibited SMC proliferation despite early induction of PDGF-A mRNA. After a delay of 24 hours, TGF-β1 increased 1α(I) procollagen expression by 36% compared with control. PDGF-neutralizing antibodies blocked the TGF-β1-mediated upregulation of type I procollagen, although PDGF alone had no effect on matrix expression. Conclusion: The results indicate that TGF-β1 is a potent inhibitor of human arterial SMC proliferation that has a moderate effect on 1α(I) procollagen transcripts. Despite inducing PDGF-A gene expressions TGF- β1 is not a mitogen in adult human arterial SMC. TGF-β1 regulates SMC type I procollagen expression partly by inducing PDGF-A as a co-factor.

Original languageEnglish (US)
Pages (from-to)767-774
Number of pages8
JournalJournal of vascular surgery
Volume23
Issue number5
DOIs
StatePublished - Jan 1 1996

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ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

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