title: Neuregulin receptor ErbB4 functions as a transcriptional cofactor for the expression of surfactant protein B in the fetal lung.
abstract: Sufficient pulmonary surfactant production is required for the fetal-neonatal transition, especially in preterm infants. Neuregulin (NRG) and its transmembrane receptor ErbB4 positively regulate the onset of fetal surfactant synthesis. Details of this signaling process remain to be elucidated. ErbB4 is known to regulate gene expression in the mammary gland, where the receptor associates with the signal transducer and activator of transcription Stat5a to transactivate the β-casein gene promoter. We hypothesized that in the fetal lung, ErbB4 functions as a transcriptional regulator for surfactant protein B (Sftpb), the most critical surfactant protein gene. Re-expressing full-length ErbB4 in primary fetal ErbB4-depleted Type II epithelial cells led to an increased expression of Sftpb mRNA. This stimulatory effect required the nuclear translocation of ErbB4 and association with Stat5a, with the resultant binding to and activation of the Sftpb promoter. We conclude that ErbB4 directly regulates important aspects of fetal lung maturation that help prepare for the fetal-neonatal transition.
authors.affiliation: Department of Pediatrics, Hannover Medical School, Hannover, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Zscheppang
authors.forename: Thilo
authors.initials: T
authors.lastname: Dörk
authors.forename: Andreas
authors.initials: A
authors.lastname: Schmiedl
authors.forename: Frank E
authors.initials: FE
authors.lastname: Jones
authors.forename: Christiane E L
authors.initials: CE
authors.lastname: Dammann
mesh_terms: D021581:Active Transport, Cell Nucleus; D056809:Alveolar Epithelial Cells / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D005865:Gestational Age; D006801:Humans; D008168:Lung / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D066247:Receptor, ErbB-4; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D020890:Neuregulin-1; D037701:Pulmonary Surfactant-Associated Protein B; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; C117467:neuregulin beta; C587689:ERBB4 protein, human; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4