TRANSCRIPTIONAL REGULATION OF TROPOELASTIN EXPRESSION IN RAT LUNG FIBROBLASTS - CHANGES WITH AGE AND HYPEROXIA

Elastic fibers are thought to provide structural support for secondary septa as the lung undergoes the transition from the saccular to the a lveolar stage. The synthesis of the soluble precursor of elastin, trop oelastin, occurs during a finite developmental period. We have investi gated the developmental regulation of tropoelastin gene transcription and mRNA expression in fetal and postnatal rat lung fibroblasts and ha ve assessed the changes in tropoelastin gene expression caused by hype roxic exposure during secondary septal development. With the use of an RT-PCR assay and intron-specific primers to detect heterogeneous nucl ear RNA (hnRNA) and intron-spanning primers to detect mRNA in freshly isolated rat lung fibroblasts, tropoelastin gene expression was found to be upregulated late in gestation. From days 18 to 21 of gestation, there was a 4.5-fold increase in tropoelastin hnRNA (P < 0.0001) and a g-fold increase in mRNA (P = 0.002). After birth, tropoelastin expres sion was downregulated. Signals decreased from fetal day 21 to postnat al day 2 for both tropoelastin hnRNA(P = 0.021) and mRNA (P = 0.043). Tropoelastin hnRNA decreased further from days 2 to 6 (P = 0.04). Both tropoelastin hnRNA and mRNA were again upregulated during alveolariza tion from days 9 to 11, indicating that, once upregulated, transcripti on of the tropoelastin gene is not constant but varies with fetal and postnatal age. Exposure to >95% oxygen, when initiated on postnatal da y 2 or 3 and continued until day 11, significantly diminished the deve lopmental increase in tropoelastin hnRNA (P < 0.005) and mRNA(P < 0.05 ) normally seen on days 9-11, indicating that the postnatal upregulati on of tropoelastin gene expression is inhibited by hyperoxic exposure in the early postnatal period.