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.
OBJECTIVE
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 1 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) procollagen 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.


CONCLUSIONS
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.
Halloran
B G
BG
Department of Surgery, University of Nebraska Medical Center, Omaha, 68198-3280, USA.
So
B J
BJ
Baxter
B T
BT
D000328:Adult; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011347:Procollagen / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*
D010982:Platelet-Derived Growth Factor; D011347:Procollagen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta