| First Author | Jaffe M | Year | 2012 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 32 |
| Issue | 1 | Pages | e1-11 |
| PubMed ID | 21979435 | Mgi Jnum | J:179089 |
| Mgi Id | MGI:5301054 | Doi | 10.1161/ATVBAHA.111.238410 |
| Citation | Jaffe M, et al. (2012) Transforming Growth Factor-beta Signaling in Myogenic Cells Regulates Vascular Morphogenesis, Differentiation, and Matrix Synthesis. Arterioscler Thromb Vasc Biol 32(1):e1-e11 |
| abstractText | OBJECTIVE: Transforming growth factor-beta (TGF-beta) signaling is required for normal vascular development. We aimed to discover the role of TGF-beta signaling in embryonic smooth muscle cells (SMCs). METHODS AND RESULTS: We bred mice with smooth muscle (SM) 22alpha-Cre and Tgfbr2(flox) alleles to generate embryos in which the type II TGF-beta receptor (TGFBR2; required for TGF-beta signaling) was deleted in SMCs. Embryos were harvested between embryonic day (E) 9.5 and E18.5 and examined grossly, microscopically, and by histochemical and RNA analyses. SM22alpha-Cre(+/0) Tgfbr2(flox/flox) (knockout [KO]) embryos died before E15.5 with defects that included cardiac outflow tract abnormalities, persistence of the right dorsal aorta, and dilation of the distal aorta. Histological analyses suggested normal expression of SMC differentiation markers in KO aortas; however, RNA analyses showed that SMC differentiation markers were increased in KO cardiac outflow vessels but decreased in the descending aorta. KO aortas had only rare mature elastin deposits and contained abnormal aggregates of extracellular matrix proteins. Expression of several matrix proteins was significantly decreased in KO descending aortas but not in cardiac outflow vessels. CONCLUSIONS: TGF-beta signaling in SMCs controls differentiation, matrix synthesis, and vascular morphogenesis. Effects of TGF-beta on SMC gene expression appear to differ depending on the location of SMCs in the aorta. |
