ErbB Receptor Regulation by Dexamethasone in Mouse Type II Epithelial Cells

¹ Dept of paediatrics, Division of Newborn Medicine, Tufts University and Floating Hospital for Children, Boston, MA 02111, U.S.A; and Dept of paediatric Pulmonology and Neonatology, Hannover Medical School, 30625 Hannover Germany
² Dept of paediatric Pulmonology and Neonatology, Hannover Medical School, 30625 Hannover Germany
³ Dept of paediatrics, Division of Newborn Medicine, Tufts University and Floating Hospital for Children, Boston, MA 02111, U.S.A

^* To whom correspondence should be addressed. E-mail: dammann.christiane{at}mh-hannover.de.

	Abstract

Glucocorticoids stimulate foetal surfactant synthesis. Therefore, they are used in impending preterm birth. One mechanism of action on surfactant synthesis is through induction of neuregulin (NRG) secretion by foetal lung fibroblasts. Direct effects on signaling pathways, specifically of erbB receptors in foetal type II cell surfactant synthesis, are less known.

We studied the effect of known promoters of foetal surfactant synthesis, namely dexamethasone and mature (i.e., NRG containing) fibroblast conditioned medium (FCM), on erbB receptor activation, protein content, and dimerization patterns in foetal mouse lung type II cells.

Dexamethasone inhibited surfactant synthesis in immature (d16) type II cells, while the mature FCM had stimulatory effects. Both treatments directly stimulated surfactant synthesis in the more mature (d17) cells. At this gestational day, dexamethasone had only a small effect on phosphorylation, but stimulated the protein content of all four erbB receptors. Dexamethasone effects were distinct from that of mature FCM, which stimulated both protein content and phosphorylation of all erbB receptors and of the signaling intermediate phospholipase C (PLC). Dexamethasone modulated erbB receptor dimerization patterns, such that erbB2 became the main dimerization partner for erbB4.

We conclude that dexamethasone signaling involves erbB receptors in foetal type II cells, similar to, but distinct from, NRG-containing FCM signaling.

Keywords:  Dimerization, epidermal growth factor, neuregulin, phospholipase C, surfactant synthesis

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