Absence of TGFbeta signaling in embryonic vascular smooth muscle leads to reduced lysyl oxidase expression, impaired elastogenesis, and aneurysm.
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.
Choudhary
Bibha
B
Zhou
Jingjing
J
Li
Peng
P
Thomas
Simmy
S
Kaartinen
Vesa
V
Sucov
Henry M
HM
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*
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