Expression of insulin-like growth factor receptors 1 and 2 in the developing lung and their relation to epithelial cell differentiation

Insulin-like growth factors (IGFs) and their receptors have been implicated as regulators of cell differentiation and cell proliferation in a number of systems and have been shown to play an important role in embryonic development. In this study we examined expression of mRNA for IGF-I and IGF-II, IGF binding protein 2 (IGFBP-2), and IGF receptors 1 (IGFR-1) and 2 (IGFR-2) during fetal lung development and in early postnatal and adult lungs by the polymerase chain reaction (PCR). IGF-I mRNA was found in embryonic and postnatal lungs at all ages as was IGFBP-2, whereas IGF-II mRNA was present only in prenatal lungs. IGFR-1 was present in all but the adult lungs. Lung epithelial cells expressed IGFR-1 at 14 days' gestation but not at 18 days' gestation as measured by PCR and in situ hybridization. Alveolar epithelial cells re-expressed IGFR-1 mRNA in the early postnatal period but not in the adult lung. IGFR-2 was expressed by PCR and in situ hybridization in 14-day embryonic epithelium, was not present at 18 days or at birth, but was re-expressed at high levels in the early postnatal alveolar wall. Immunocytochemical localization of IGFR-2 confirmed its absence in the late fetal and newborn lung. It reappeared in alveoli, exclusively in type 1 cells, in early postnatal and adult lungs. These studies demonstrate the stage- and cell-specific appearance of IGF receptors in the developing and postnatal lung. They also establish IGFR-2 as a marker of the mature alveolar type 1 cell.