The role of integrin alpha8beta1 in fetal lung morphogenesis and injury.
Prenatal inflammation prevents normal lung morphogenesis and leads to bronchopulmonary dysplasia (BPD), a common complication of preterm birth. We previously demonstrated in a bacterial endotoxin mouse model of BPD that disrupting fibronectin localization in the fetal lung mesenchyme causes arrested saccular airway branching. In this study we show that expression of the fibronectin receptor, integrin alpha8beta1 is decreased in the lung mesenchyme in the same inflammation model suggesting it is required for normal lung development. We verified a role for integrin alpha8beta1 in lung development using integrin alpha8-null mice, which develop fusion of the medial and caudal lobes as well as abnormalities in airway division. We further show in vivo and in vitro that alpha8-null fetal lung mesenchymal cells fail to form stable adhesions and have increased migration. Thus we propose that integrin alpha8beta1 plays a critical role in lung morphogenesis by regulating mesenchymal cell adhesion and migration. Furthermore, our data suggest that disruption of the interactions between extracellular matrix and integrin alpha8beta1 may contribute to the pathogenesis of BPD.
Benjamin
John T
JT
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232-0493, USA.
Gaston
David C
DC
Halloran
Brian A
BA
Schnapp
Lynn M
LM
Zent
Roy
R
Prince
Lawrence S
LS
D000818:Animals; D002465:Cell Movement; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D016023:Integrins / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000502:physiology*; D016133:Polymerase Chain Reaction
D016023:Integrins; D008070:Lipopolysaccharides; C094866:integrin alpha8beta1