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

被引:15
作者
Halloran, BG
So, BJ
Baxter, BT
机构
[1] UNIV NEBRASKA,MED CTR,DEPT SURG,OMAHA,NE 68198
[2] WON KWANG UNIV,DEPT GEN SURG,SEOUL,SOUTH KOREA
关键词
D O I
10.1016/S0741-5214(96)70238-0
中图分类号
R61 [外科手术学];
学科分类号
摘要
Purpose: Depending on the derivation of vascular smooth muscle cells (SMC), transforming growth factor-beta 1 (TGF-beta 1) has variable effects on proliferation and expression of extracellular matrix. Relatively little is known about TGF-beta 1's effects on human arterial SMC. Therefore, we sought to determine the effects of TGF-beta 1 on human arterial SMC proliferation and l alpha(I) procollagen expression. The mechanisms by which TGF-beta 1 regulate type I procollagen expression were also investigated. Methods: SMC cultures were established from the aorta of transplant donors. Serial doses of TGF-beta 1 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 1 alpha(I) procol lagen and platelet-derived growth factor (PDGF)-A transcripts. Results: In a dose-dependent manner, TGF-beta 1 inhibited SMC proliferation despite early induction of PDGF-A mRNA. After a delay of 24 hours, TGF-beta 1 increased 1 alpha(I) procollagen expression by 36% compared with control. PDGF-neutralizing antibodies blocked the TGF-beta 1-mediated upregulation of type I procollagen, although PDGF alone had no effect on matrix expression. Conclusion: The results indicate that TGF-beta 1 is a potent inhibitor of human arterial SMC proliferation that has a moderate effect on 1 alpha(I) procollagen transcripts. Despite inducing PDGF-A gene expression, TGF-beta 1 is not a mitogen in adult human arterial SMC. TGF-beta 1 regulates SMC type I procollagen expression partly by inducing PDGF-A as a co-factor.
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页码:767 / 773
页数:7
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