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

Purpose: Depending on the derivation of vascular smooth muscle cells ( SMC), transforming growth factor-beta 1 (TGF-beta 1) has variable effe cts on proliferation and expression of extracellular matrix. Relativel y little is known about TGF-beta 1's effects on human arterial SMC. Th erefore, we sought to determine the effects of TGF-beta 1 on human art erial SMC proliferation and l alpha(I) procollagen expression. The mec hanisms by which TGF-beta 1 regulate type I procollagen expression wer e also investigated. Methods: SMC cultures were established from the a orta of transplant donors. Serial doses of TGF-beta 1 were applied, an d cellular proliferation assessed by cell counting and tritiated thymi dine 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 fac tor (PDGF)-A transcripts. Results: In a dose-dependent manner, TGF-bet a 1 inhibited SMC proliferation despite early induction of PDGF-A mRNA . After a delay of 24 hours, TGF-beta 1 increased 1 alpha(I) procollag en expression by 36% compared with control. PDGF-neutralizing antibodi es blocked the TGF-beta 1-mediated upregulation of type I procollagen, although PDGF alone had no effect on matrix expression. Conclusion: T he results indicate that TGF-beta 1 is a potent inhibitor of human art erial SMC proliferation that has a moderate effect on 1 alpha(I) proco llagen transcripts. Despite inducing PDGF-A gene expression, TGF-beta 1 is not a mitogen in adult human arterial SMC. TGF-beta 1 regulates S MC type I procollagen expression partly by inducing PDGF-A as a co-fac tor.