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Regulation of vascular smooth muscle cell integrin expression by transforming growth factor β1 and by platelet-derived growth factor-BB

✍ Scribed by M. Fouad Janat; W. Scott Argraves; Gene Liau


Publisher
John Wiley and Sons
Year
1992
Tongue
English
Weight
880 KB
Volume
151
Category
Article
ISSN
0021-9541

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✦ Synopsis


We have examined the ability of transforming growth factor-pl (TGF-p1) 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 a,p3 integrin complex was induced by both growth factors, although TGF-PI appeared to be the more potent inducer. mRNA level of the p3 integrin subunit was undetectable in quiescent cells and enhanced by both growth factors, while the a, integrin subunit mRNA level did not change with growth factor addition. Therefore, appearance of the a& integrin protein complex after growth factor stimulation was due to increased expression of thc P3 integrin subunit mRNA. The TGF-Pl induced increase in p3 integrin mRNA was delaycd, but did not require prior protein synthesis, since cycloheximide was unable to block the increase in p3 mRNA level. By contrast, PDGF-BB induced a more rapid increase in p3 integrin mRNA level that peaked by 6 h after growth factor addition and no detectable p3 integrin mRNA remained after 24 h. Interestingly, the PDCF-BB induced elevation of p3 integrin, although more rapid, was completely inhibited by cycloheximide. Expression of the a5 integrin subunit in response to growth factors was very similar to p3. However, in contrast to p3 and as, neither TCF-pl nor PDGF-BB were able to alter the expression of the pi inlegrin subunit in vascular SMC. However, in TGF-PI treated cells, there was a large increase in expression of a 190 kDa polypeptide that was associated with the p, integrin subunit. This 190 kDa polypeptide was not detected in PDGF treated SMC or in TGF-pl treated fibroblasts. The a , integrin subunit has a M W of approximately 190 kDa and is capable of complexing with pi. Analysis of the a , integrin subunit mRNA level indicated that it was indeed induced by TGF-P1, but not by PDCF-BB, suggesting that the 190 kDa polypeptide may be the mi integrin subunit. Thcsc results indicate that TGF-Pl and PDGF-BB are potent but distinct activators of integrin expression in vascular SMC. o 1992 Wilev-Liss. Inc.


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