Transforming Growth Factor-α Gene Expression in Late-Gestation Fetal Rat Lung

Abstract

ABSTRACT. Transforming growth factor-a (TGF-a) is a structural homologue of epidermal growth factor and competes for binding on a common transmembrane protein receptor/kinase. Although TGF-a appears to be more important than epidermal growth factor in embryogenesis and mammalian organogenesis, there is little information regarding its expression in developing lung. Accordingly, we measured levels of immunoreactive TGF-a and its gene expression in late-term fetal rat lung during the transition from the canalicular (19-20 d) to the saccular (21 d) stage. We report that at 19 d gestation intrapulmonary levels of TGF-a were 1.4 f 0.3 pmol/mg protein as determined by RIA, but had decreased by 50% at 21 d. To determine if the TGF-a gene is expressed in lung, RNA isolated from fetal rat lung was reverse transcribed, and a 302-bp fragment corresponding to a portion of the TGF-a gene was amplified by polymerase chain reaction. Southern blot hybridization with a 32P-labeled 2.3-kb EcoRI fragment of rat TGF-a cDNA clone showed a pattern of declining expression during late gestation. Therefore, fetal rat lung expresses TGF-a, as is evidenced by the synthesis of both the message and the protein. Because levels of protein were highest in the period of canalicular lung development when the respiratory acinus is formed and vascularized, a potential role for this intrapulmonary growth factor in pulmonary remodeling is suggested. (Pediatr Res 31: 286-290,1992) Abbreviations TGF-a, transforming growth factor-a EGF, epidermal growth factor EGF-R, epidermal growth factor receptor IR-TGF-a, immuno reactive TGF-a PCR, polymerase chain reaction SSC, sodium chloride, sodium citrate sus has grown that TGF-a, and not EGF, is the more abundant, and perhaps critical, fetal growth factor of the two (4-7).It seems likely that the above growth factors play an important role in fetal lung development as well. EGF receptors are abundant in fetal lung tissue (8-lo), and exogenous EGF can 1 ) stimulate proliferation of epithelial cells in conducting airways of fetal lambs in vivo (1 1) and fetal human epithelial type I1 cells in vitro (12), 2 ) accelerate lung maturation of fetal rabbits in vivo (8) and rat alveolar epithelial cells in vitro (13,14), and 3 ) accelerate differentiation of tracheal mucous secretory cells in fetal rhesus monkey in utero (15). Despite the widespread distribution of EGF-R in the fetal lung and the effectiveness of exogenous EGF, relatively little is known about endogenous ligands for the EGF-R. EGF precursor mRNA and epitopes common to this precursor have been localized to the developing mouse lung by using in situ hybridization and immunodetection techniques, respectively, and confirmed with PCR detection of fetal mouse lung EGF precursor RNA (37). In late gestational human lung, immunoreactive EGF is limited to nonmucous cells of the submucosal glands of the upper airways (1 6). In fetal sheep, a novel alternative EGF-R ligand, lipocortin-1, has been immunolocalized in airway epithelium (10).We were interested in...

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