ErbB4 regulates fetal surfactant phospholipid synthesis in primary fetal rat type II cells

• Published in: American journal of physiology. Lung cellular and molecular physiology 2007-08, Vol.293 (2), p.L429-L435
• Main Authors: Zscheppang, Katja, Liu, Washa, Volpe, MaryAnn V, Nielsen, Heber C, Dammann, Christiane E. L
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation - physiology; Cell Division - physiology; Cells; Choline - pharmacokinetics; Dimerization; Down-Regulation - physiology; Epithelial Cells - cytology; Epithelial Cells - metabolism; Female; Lung - cytology; Lung - embryology; Lungs; Phospholipids - metabolism; Pregnancy; Pulmonary Surfactants - metabolism; Rats; Rats, Sprague-Dawley; Receptor, Epidermal Growth Factor - chemistry; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Receptor, ErbB-4; Respiratory Mucosa - cytology; Respiratory Mucosa - embryology; Ribonucleic acid; RNA; RNA, Small Interfering; Rodents; T cell receptors; Thymidine - pharmacokinetics
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00451.2006

1 Department of Pediatrics, Division of Newborn Medicine, Tufts University and Floating Hospital for Children, Boston, Massachusetts; 2 University of Applied Sciences Lausitz, Senftenberg, Germany; and 3 Department of Pediatric Pulmonology and Neonatology, Hannover Medical School, Hannover, Germany Submitted 16 November 2006 ; accepted in final form 31 May 2007 Insufficient fetal surfactant production leads to respiratory distress syndrome among preterm infants. Neuregulin signals the onset of fetal surfactant phospholipid synthesis through formation of erbB receptor dimers. We hypothesized that erbB4 downregulation in fetal type II epithelial cells will downregulate not only fetal surfactant phospholipid synthesis, but also affect proliferation and erbB receptor localization. We tested these hypotheses using small interfering RNA (siRNA) directed against the erbB4 gene to silence erbB4 receptor function in cultures of primary day 19 fetal rat lung type II cells. ErbB4 siRNA treatment inhibited erbB4 receptor protein expression, fibroblast-conditioned medium induced erbB4 phosphorylation, and fetal surfactant phospholipid synthesis. Cell proliferation, measured as thymidine incorporation, was also inhibited by erbB4 siRNA treatment. Downregulation of erbB4 receptor protein changed erbB1 localization at baseline and after stimulation, as determined by confocal microscopy and subcellular fractionation. We conclude that erbB4 is an important receptor in the control of fetal lung type II cell maturation. small interfering RNA Address for reprint requests and other correspondence: C. E. L. Dammann, Dept. of Pediatrics, Tufts New England Medical Center, 750 Washington St., Boston, MA 02111 (e-mail: cdammann{at}tufts-nemc.org )