TGF-beta signaling is dynamically regulated during the alveolarization of rodent and human lungs.
Although transforming growth factor-beta (TGF-beta) signaling negatively regulates branching morphogenesis in early lung development, few studies to date have addressed the role of this family of growth factors during late lung development. We describe here that the expression, tissue localization, and activity of components of the TGF-beta signaling machinery are dynamically regulated during late lung development in the mouse and human. Pronounced changes in the expression and localization of the TGF-beta receptors Acvrl1, Tgfbr1, Tgfbr2, Tgfbr3, and endoglin, and the intracellular messengers Smad2, Smad3, Smad4, Smad6, and Smad7 were noted as mouse and human lungs progressed through the canalicular, saccular, and alveolar stages of development. TGF-beta signaling, assessed by phosphorylation of Smad2, was detected in the vascular and airway smooth muscle, as well as the alveolar and airway epithelium throughout late lung development. These data suggest that active TGF-beta signaling is required for normal late lung development.
Alejandre-Alcázar
Miguel A
MA
Department of Internal Medicine, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany.
Michiels-Corsten
Matthias
M
Vicencio
Alfin G
AG
Reiss
Irwin
I
Ryu
Julie
J
de Krijger
Ronald R
RR
Haddad
Gabriel G
GG
Tibboel
Dick
D
Seeger
Werner
W
Eickelberg
Oliver
O
Morty
Rory E
RE
D030201:Activin Receptors, Type I / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D030301:Activin Receptors, Type II / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000818:Animals; D000071063:Endoglin; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008168:Lung / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051905:Smad6 Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D051905:Smad6 Protein; C497803:Smad6 protein, mouse; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D016212:Transforming Growth Factor beta; C071736:betaglycan; D017346:Protein Serine-Threonine Kinases; C425364:ACVRL1 protein, human; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II; C498931:Acvrl1 protein, mouse; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625841:TGFBR1 protein, human; C000625842:Tgfbr1 protein, mouse