REGULATION OF VASCULAR SMOOTH-MUSCLE CELL INTEGRIN EXPRESSION BY TRANSFORMING GROWTH FACTOR-BETA-1 AND BY PLATELET-DERIVED GROWTH FACTOR-BB

We have examined the ability of transforming growth factor-beta-1 (TGF-beta-1) and platelet-derived growth factor-BB (PDGF-BB) to regulate the expression of various integrins in cultured rabbit vascular smooth muscle cells (SMC). We found that expression of the alpha(v)beta-3 integrin complex was induced by both growth factors, although TGF-beta-1 appeared to be the more potent inducer. mRNA level of the beta-3 integrin subunit was undetectable in quiescent cells and enhanced by both growth factors, while the alpha(v) integrin subunit mRNA level did not change with growth factor addition. Therefore, appearance of the alpha(v)beta-3 integrin protein complex after growth factor stimulation was due to increased expression of the beta-3 integrin subunit mRNA. The TGF-beta-1 induced increase in beta-3 integrin mRNA was delayed, but did not require prior protein synthesis, since cycloheximide was unable to block the increase in beta-3 mRNA level. By contrast, PDGF-BB induced a more rapid increase in beta-3 integrin mRNA level that peaked by 6 h after growth factor addition and no detectable beta-3 integrin mRNA remained after 24 h. Interestingly, the PDGF-BB induced elevation of beta-3 integrin, although more rapid, was completely inhibited by cycloheximide. Fxpression of the alpha-5 integrin subunit in response to growth factors was very similar to beta-3. However, in contrast to beta-3 and alpha-5, neither TGF-beta-1 nor PDGF-BB were able to alter the expression of the beta-1 integrin subunit in vascular SMC. However, in TGF-beta-1 treated cells, there was a large increase in expression of a 190 kDa polypeptide that was associated with the beta-1 integrin subunit. This 190 kDa polypeptide was not detected in PDGF treated SMC or in TGF-beta-1 treated fibroblasts. The alpha-1 integrin subunit has a MW of approximately 190 kDa and is capable of complexing with beta-1. Analysis of the alpha-1 integrin subunit mRNA level indicated that it was indeed induced hy TGF-beta-1, but not by PDGF-BB, suggesting that the 1 90 kDa polypeptide may be the alpha-1 integrin subunit. These results indicate that TGF-beta-1 and PDGF-BB are potent but distinct activators of integrin expression in vascular SMC.