Differential Response of Mesoderm- and Neural Crest-Derived Smooth Muscle to TGF-β1: Regulation of c-myb and α1 (I) Procollagen Genes

Previously, we demonstrated that avian vascular smooth muscle cells (VSMC) derived from embryonic abdominal and thoracic aorta grow differently in the presence of transforming growth factor beta (TGF-β1) and platelet-derived growth factor (PDGF-BB) (Wrenn et al., In Vitro Cell. Dev. Biol.29, 73–78, 1992). The thoracic VSMC (N-VSMC) are derived from neural crest, and therefore differentiate from ectoderm; the abdominal VSMC (M-VSMC) are derived from mesoderm. The present study was designed to identify factors that mediate the differential responses of the VSMC to TGF-β1. We found that TGF-β1 increased DNA synthesis by approximately sevenfold in N-VSMC. Levels of both α1 (I) procollagen and c-myb mRNAs were markedly induced in N-VSMC treated with TGF-β1. Chimeric plasmids containing up to 3.5 kb of α1 (I) procollagen 5′ flanking DNA were induced to equivalent levels as procollagen mRNA in N-VSMC. However, TGF-β1 increased DNA synthesis by threefold in M-VSMC; there was no effect on α1 (I) procollagen expression, and c-myb was not expressed, as demonstrated by immunohistochemistry staining and RNA analyses. Antisense c-myb oligodeoxynucleotides blocked the TGF-β1 induction of α1 (I) procollagen and the growth of N-VSMC. The increase in DNA synthesis by M- and N-VSMC was correlated with the secretion of PDGF-AA, and staurosporine and antibodies directed against PDGF-AA suppressed DNA synthesis. Our results demonstrate that TGF-β1 activity and c-myb expression modulate the expression of α1 (I) collagen and cell proliferation in neural crest-derived smooth muscle. The regulation of these events by TGF-β1 may be important during morphogenesis of blood vessels and vascular diseases.