title: Transforming growth factor-β signaling in myogenic cells regulates vascular morphogenesis, differentiation, and matrix synthesis.
abstract: OBJECTIVE
  Transforming growth factor-β (TGF-β) signaling is required for normal vascular development. We aimed to discover the role of TGF-β signaling in embryonic smooth muscle cells (SMCs).
  
  
  RESULTS
  We bred mice with smooth muscle (SM) 22α-Cre and Tgfbr2(flox) alleles to generate embryos in which the type II TGF-β receptor (TGFBR2; required for TGF-β 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. SM22α-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-β signaling in SMCs controls differentiation, matrix synthesis, and vascular morphogenesis. Effects of TGF-β on SMC gene expression appear to differ depending on the location of SMCs in the aorta.
authors: Division of Cardiology, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
authors: Mia
authors: M
authors: Jaffe
authors: Casilde
authors: C
authors: Sesti
authors: Ida M
authors: IM
authors: Washington
authors: Liang
authors: L
authors: Du
authors: Nagadhara
authors: N
authors: Dronadula
authors: Michael T
authors: MT
authors: Chin
authors: Donna B
authors: DB
authors: Stolz
authors: Elaine C
authors: EC
authors: Davis
authors: David A
authors: DA
authors: Dichek
mesh_terms: D000818:Animals; D001011:Aorta / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism; D001808:Blood Vessels / Q000196:embryology; D002454:Cell Differentiation / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024510:Muscle Development / Q000502:physiology; D032390:Myoblasts, Smooth Muscle / Q000166:cytology* / Q000502:physiology*; D018919:Neovascularization, Physiologic; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D016326:Extracellular Matrix Proteins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II