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.
journal_name
Am J Respir Cell Mol Biolauthors
Zscheppang K,Dörk T,Schmiedl A,Jones FE,Dammann CEdoi
10.1165/rcmb.2010-0179OCsubject
Has Abstractpub_date
2011-10-01 00:00:00pages
761-7issue
4eissn
1044-1549issn
1535-4989pii
2010-0179OCjournal_volume
45pub_type
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