title: Differential response of mesoderm- and neural crest-derived smooth muscle to TGF-beta1: regulation of c-myb and alpha1 (I) procollagen genes.
abstract: 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-beta1) 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-beta1. We found that TGF-beta1 increased DNA synthesis by approximately sevenfold in N-VSMC. Levels of both alpha1 (I) procollagen and c-myb mRNAs were markedly induced in N-VSMC treated with TGF-beta1. Chimeric plasmids containing up to 3.5 kb of alpha1 (I) procollagen 5' flanking DNA were induced to equivalent levels as procollagen mRNA in N-VSMC. However, TGF-beta1 increased DNA synthesis by threefold in M-VSMC; there was no effect on alpha1 (I) procollagen expression, and c-myb was not expressed, as demonstrated by immunohistochemistry staining and RNA analyses. Antisense c-myb oligodeoxynucleotides blocked the TGF-beta1 induction of alpha1 (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-beta1 activity and c-myb expression modulate the expression of alpha1 (I) collagen and cell proliferation in neural crest-derived smooth muscle. The regulation of these events by TGF-beta1 may be important during morphogenesis of blood vessels and vascular diseases.
authors.affiliation: Department of Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha 68195-6395, USA.
authors.forename: P F
authors.initials: PF
authors.lastname: Gadson
authors.forename: M L
authors.initials: ML
authors.lastname: Dalton
authors.forename: E
authors.initials: E
authors.lastname: Patterson
authors.forename: D D
authors.initials: DD
authors.lastname: Svoboda
authors.forename: L
authors.initials: L
authors.lastname: Hutchinson
authors.forename: D
authors.initials: D
authors.lastname: Schram
authors.forename: T H
authors.initials: TH
authors.lastname: Rosenquist
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000166:cytology / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D001717:Birds / Q000196:embryology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D008648:Mesoderm; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011347:Procollagen / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger; D013936:Thymidine / Q000493:pharmacokinetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D010982:Platelet-Derived Growth Factor; D011347:Procollagen; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D013936:Thymidine