Transforming growth factor-beta inhibits human vascular smooth muscle cell growth and migration.
BACKGROUND
Transforming growth factor-beta (TGF-beta) is released after vascular injury and may influence the healing response of the vessel wall. We investigated the effect of this growth factor on proliferation and migration of human venous smooth muscle cells (SMC) and the signal transduction mechanisms through which TGF-beta exerts this effect.


METHODS
SMC derived from human saphenous vein were used in a 72-hour proliferation assay and a 6-day migration assay. Cells were exposed to TGF-beta alone and in the presence of platelet-derived growth factor (PDGF), basic fibroblast growth factor (b-FGF), epidermal growth factor, and serum. The ability of TGF-beta to activate tyrosine kinases, phosphatases, or protein kinase C was evaluated by use of Western blotting with an antiphosphotyrosine antibody.


RESULTS
In a concentration-dependent manner, TGF-beta inhibited proliferation induced by PDGF, b-FGF, epidermal growth factor, and serum. This inhibitory effect was independent of SMC density. TGF-beta also inhibited migration induced by PDGF and b-FGF. Exposure of cells to TGF-beta did not lead to tyrosine phosphorylation of cellular substrates or activation of protein kinase C.


CONCLUSIONS
TGF-beta inhibits both migration and proliferation of human SMC. This inhibitory effect is not mediated through protein kinase C, mitogen-activated protein kinase, or tyrosine kinases.
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Department of Surgery, Beth Israel Hospital, Harvard Medical School, Boston, Mass. 02215.
Ware
J A
JA
Kent
K C
KC
D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011493:Protein Kinase C / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases