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Strain‐induced fetal type II epithelial cell differentiation is mediated via cAMP‐PKA‐dependent signaling pathway
Author(s) -
Wang Yulian,
Maciejewski Benjamin S.,
Lee Nicole,
Silbert Ophira,
Mcknight Nathan L.,
Frangos John A.,
SanchezEsteban Juan
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb41-a
Subject(s) - forskolin , creb , heterotrimeric g protein , signal transduction , camp dependent pathway , protein kinase a , microbiology and biotechnology , biology , cellular differentiation , adenylate kinase , chemistry , endocrinology , g protein , medicine , phosphorylation , transcription factor , receptor , biochemistry , stimulation , gene
The signaling pathways by which mechanical forces modulate fetal lung development remain largely unknown. In the present study, we tested the hypothesis that strain‐induced fetal type II cell differentiation is mediated via cAMP signaling pathway. Freshly isolated E19 fetal type II epithelial cells were cultured on collagen‐coated silastic membranes and exposed to mechanical strain for varying intervals, to simulate mechanical forces in utero. Unstretched samples were used as controls. Mechanical strain activated heterotrimeric G‐protein α s subunit, cAMP and the transcription factor CREB. Moreover, adenylate cyclase 5 and CREB genes were also mechanically induced. In contrast, components of the PKA‐independent (Epac) pathway, including Rap‐1 or B‐Raf, were not phosphorylated by strain. The addition of forskolin to unstretched E19 monolayers markedly upregulated expression of the type II cell differentiation marker surfactant protein‐C (SP‐C), whereas the Epac agonist 8‐pCPT‐2′‐O‐Me‐cAMP had no effect. Incubation of E19 cells with PKA inhibitors significantly decreased strain‐induced CREB phosphorylation and SP‐C mRNA expression. In conclusion, these studies indicate that cAMP‐PKA‐dependent signaling pathway is activated by force in fetal type II cells and participates in strain‐induced fetal type II cell differentiation. This work was supported by National Institutes of Health Grants RR‐018728 and Parker B. Francis.