EXPRESSION OF TRANSFORMING GROWTH FACTOR-ALPHA IN MIDGESTATION HUMAN FETAL LUNG

Transforming growth factor-alpha (TGF-alpha), a member of the epiderma l growth factor (EGF) family, is a potent mitogen for several cell typ es. To investigate the possible role of TGF-alpha in the development o f mid-gestation human fetal lung, we studied its distribution with imm unohistochemistry and determined levels of steady-state TGF-alpha mRNA by Northern analysis of cellular RNA isolates from lung. Lung was obt ained from fetuses at 10 to 22 wk of gestation (n = 14) and immunostai ned for TGF-alpha. TGF-alpha was localized in epithelial cells at all gestational ages examined. Immunostaining was particularly prominent i n bronchiolar epithelial cells. TGF-alpha immunoreactivity was also as sociated with arterial smooth muscle cells, as well as with nerves. Oc casional chondrocytes were also associated with TGF-alpha immunoreacti vity. Total cellular RNA was isolated from lung tissue obtained from a dditional fetuses at gestational ages 10 to 24 wk (n = 22). TGF-alpha mRNA was present in RNA extracts of all fetal lungs studied. We conclu de that TGF-alpha is probably produced in human fetal lung during mid- gestation. The prominent immunostaining of bronchiolar epithelial cell s for TGF-alpha is consistent with its playing a role in distal airway formation.