EXPRESSION AND LOCALIZATION OF EPIDERMAL GROWTH-FACTOR, TRANSFORMING GROWTH-FACTOR-ALPHA, AND LOCALIZATION OF THEIR COMMON RECEPTOR IN FETAL HUMAN LUNG DEVELOPMENT

Transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), and their common EGF receptor have been shown to be involved in cell proliferation and lung maturation. The aim of the study was to d etermine the site of production of TGF-alpha and EGF mRNA and the cell ular distribution of TGF-alpha/EGF proteins and EGF receptor, in fetal human lung. By using in situ hybridization with S-35-labeled cDNA pro bes in frozen sections from eight lungs from fetuses ranging from 12 t o 33 wk of gestation, TGF-alpha and EGF mRNA transcripts appeared to b e confined to the mesenchymal cells and mainly found in the dense conn ective tissue along the pleura, bronchi, and large vessels, but undete cted in bronchial epithelial cells. The streptavidin-biotin immunopero xidase method, applied to paraffin-embedded specimens from 39 fetuses ranging from 10 to 41 wk, showed that TGF-alpha, EGF, and EGF receptor exhibited a similar cellular distribution during the whole period of gestation. They were detected in the undifferentiated cells of the air way surface epithelium, mesothelial cells, smooth muscle, and a few me senchymal cells, as early as 10 wk. After 12 wk, the immunoreactivity was strong in the ciliated, secretory, and basal cells, and in growing glands along the large airways, but proved lower in the the distal ai rways. After 24 wk, the immunoreactivity remained in the airway epithe lium, but was mainly localized in the apical domain of ciliated cells, in alveolar cells, and in the serous cells of the glands. The presenc e of TGF-alpha, EGF, and EGF receptor during the whole period of fetal lung development suggests that these factors are not only mitogenic, but can also be involved in epithelial maturation, through paracrine s ecretion, as most TGF-alpha and EGF mRNA transcripts are expressed in mesenchymal cells.