title: Absence of TGFbeta signaling in embryonic vascular smooth muscle leads to reduced lysyl oxidase expression, impaired elastogenesis, and aneurysm.
abstract: To address the requirement for TGFbeta signaling in the formation and maintenance of the vascular matrix, we employed lineage-specific mutation of the type II TGFbeta receptor gene (Tgfbr2) in vascular smooth muscle precursors in mice. In both neural crest- and mesoderm-derived smooth muscle, absence of TGFbeta receptor function resulted in a poorly organized vascular elastic matrix in late-stage embryos which was prone to dilation and aneurysm. This defect represents a failure to initiate formation of the elastic matrix, rather than a failure to maintain a preexisting matrix. In mutant tissue, lysyl oxidase expression was substantially reduced, which may contribute to the observed pathology.
authors.forename: Bibha
authors.initials: B
authors.lastname: Choudhary
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhou
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Simmy
authors.initials: S
authors.lastname: Thomas
authors.forename: Vesa
authors.initials: V
authors.lastname: Kaartinen
authors.forename: Henry M
authors.initials: HM
authors.lastname: Sucov
mesh_terms: D000783:Aneurysm / Q000196:embryology* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004547:Elastic Tissue / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism*; D009154:Mutation; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D012313:RNA; D008249:Protein-Lysine 6-Oxidase; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse