Regulation of the G protein Galphai2 by growth and development in fetal airway epithelium

Heterotrimeric guanine nucleotide-binding (G) proteins transduce a wide variety of receptor-mediated signals to effectors that are involved in numerous cellular functions, including cell proliferation and differentiation. Thrombin and bombesin/gastrin-releasing peptide mediate their effects via G protein-coupled receptors to regulate lung growth and development. The growth responses of these ligands are likely to be mediated via the Gi subfamily of G proteins, specifically via Galphai2. We hypothesized that Galphai2 is expressed in the lung during ontogeny in a growth-dependent manner, and that Galphai2 regulates cell growth. We demonstrate that Galphai2 is present in the developing lung of Sprague-Dawley rats, and that its expression is enhanced between embryonic Day 19 and postnatal Day 2. The strongest expression occurs in the fetal airway epithelium, and this expression in fetal airway cells is growth-dependent. Galphai2 is localized to the plasma membrane, a location consistent with interaction with growth factor receptors. Inhibition of Gi-family signal transduction by pertussis toxin (10 ng/ml) inhibits DNA synthesis in embryonic Day 19 in fetal airway epithelium. Galphai2 is likely to be a key mediator of growth signals in the developing lung.