Smooth muscle cell phenotype-dependent transcriptional regulation of the alpha 1 integrin gene

The expressional regulation of chicken alpha 1 integrin in smooth muscle cells was studied. The alpha 1 integrin mRNA was expressed developmentally and was distributed dominantly in vascular and visceral smooth muscles in chick embryos. In a primary culture of smooth muscle cells, alpha 1 integrin expression was dramatically down-regulated during serum-induced dedifferentiation. Promoter analyses revealed that the 5'-upstream region (-516 to +281) was sufficient for transcriptional activation in differentiated smooth muscle cells but not in dedifferentiated smooth muscle cells or chick embryo fibroblasts. Like other alpha integrin promoters, the promoter region of the alpha 1 integrin gene lacks TATA and CCAAT boxes and contains binding sites for AP1 and AP2. The essential difference from other alpha integrin promoters is the presence of a CArG box-like motif. Deletion and site-directed mutation analyses revealed that the CArG box-like motif was an essential cis-element for transcriptional activation in differentiated smooth muscle cells, whereas the binding sites for AP1 and AP2 were not. Using specific antibodies, a nuclear protein factor specifically bound to the CArG; box-like motif was identified as serum response factor. These results indicate that (yl integrin expression in smooth muscle cells is regulated transcriptionally in a phenotype-dependent manner and that serum response factor binding plays a crucial role in this regulation.