ErbB4 deletion leads to changes in lung function and structure similar to bronchopulmonary dysplasia.
Neuregulin is an important growth factor in fetal surfactant synthesis, and downregulation of its receptor, ErbB4, impairs fetal surfactant synthesis. We hypothesized that pulmonary ErbB4 deletion will affect the developing lung leading to an abnormal postnatal lung function. ErbB4-deleted lungs of 11- to 14-wk-old adult HER4heart mice, rescued from their lethal cardiac defects, were studied for the effect on lung function, alveolarization, and the surfactant system. ErbB4 deletion impairs lung function and structure in HER4heart mice resulting in a hyperreactive airway system and alveolar simplification, as seen in preterm infants with bronchopulmonary dysplasia. It also leads to a downregulation of surfactant protein D expression and an underlying chronic inflammation in these lungs. Our findings suggest that this animal model could be used to further study the pathogenesis of bronchopulmonary dysplasia and might help design protective interventions.
Purevdorj
Erkhembulgan
E
Department of Pediatric Pulmonology and Neonatology, Hannover Medical School, Hannover, Germany.
Zscheppang
Katja
K
Hoymann
Heinz G
HG
Braun
Armin
A
von Mayersbach
Dietlinde
D
Brinkhaus
Maria-Jantje
MJ
Schmiedl
Andreas
A
Dammann
Christiane E L
CE
D000818:Animals; D001997:Bronchopulmonary Dysplasia / Q000503:physiopathology*; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000172:deficiency* / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000473:pathology* / Q000503:physiopathology* / Q000648:ultrastructure; D051379:Mice; D037663:Pulmonary Surfactant-Associated Protein D / Q000096:biosynthesis; D066247:Receptor, ErbB-4
D037663:Pulmonary Surfactant-Associated Protein D; C587689:ERBB4 protein, human; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4