Differential response of mesoderm- and neural crest-derived smooth muscle to TGF-beta 1: Regulation of c-myb and alpha 1 (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-beta 1) 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-beta 1. We found that TGF-beta 1 increased DNA synthesis by approximately sevenfold in N-VSMC. Levels of both alpha 1 (I) procollagen and c-myb mRNAs were markedly induced in N-VSMC treated with TGF-beta 1. Chimeric plasmids containing up to 3.5 kb of alpha 1 (I) procollagen 5' flanking DNA were induced to equivalent levels as procollagen mRNA in N-VSMC. However, TGF-beta 1 increased DNA synthesis by threefold in M-VSMC; there was no effect on alpha 1 (I) procollagen expression, and c-myb was not expressed, as demonstrated by immunohistochemistry staining and RNA analyses. Antisense c-myb oligodeoxynucleotides blocked the TGF-beta 1 induction of alpha 1 (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-beta 1 activity and c-myb expression modulate the expression of alpha 1 (I) collagen and cell proliferation in neural crest-derived smooth muscle. The regulation of these events by TGF-beta 1 may be important during morphogenesis of blood vessels and vascular diseases. (C) 1997 Academic Press.