Tracheal occlusion in fetal rats alters expression of mesenchymal nuclear transcription factors without affecting surfactant protein expression

Abstract

Background/Purpose Mesenchymal nuclear transcription factors (MNTF) are involved in lung development and maturation and regulate surfactant protein (SP) expression. Prolonged (>2 weeks) fetal tracheal occlusion (TO) has been shown to accelerate lung growth and inhibit pulmonary surfactant synthesis. The effects of TO on SP expression and MNTF, however, have not been formally assessed. The objectives of this study were to evaluate the effects of short-term (3 days) TO on normal lung growth and protein expression of pulmonary MNTF involved in SP synthesis. Methods At E19 (term, 22 days), 2 fetuses per time-dated Sprague-Dawley rats underwent either TO (n = 23) or a sham (n = 22) operation. Lungs were harvested 72 hours post surgery. Pulmonary SP-A; SP-B; SP-C messenger RNA (mRNA) expression; and SP-A and SP-B, Hoxb5, thyroid transcription factor 1, and retinoic X receptor– α protein expression were analyzed. Results Lung weight was significantly increased by TO (TO 0.32 ± 0.02g vs SHAM 0.14 ± 0.01 g; P < .001), resulting in 123% increase of the lung-to-body-weight ratio. No difference of SP-A-mRNA (177 ± 4.3 TO vs 169 ± 4.4 SHAM; P = .25), SP-B-mRNA (87.7 ± 0.2 TO vs 87.4 ± 0.02 SHAM; P = .33), and SP-C-mRNA (186.5 ± 3.2 TO vs 183.2 ± 2.7 SHAM; P = .45) expression was found. Surfactant protein A (175.6 ± 25.3 TO vs 192.5 ± 19.8 SHAM; P = .59) and SP-B (163.4 ± 5.2 TO vs 166.8 ± 9.3 SHAM; P = .75) protein expression were similar in both groups; however, Hoxb5 (70.3 ± 18.9 TO vs 130.6 ± 5.1 SHAM; P = .02) and thyroid transcription factor 1 (102.6 ± 19 TO vs 181.1 ± 6.3 SHAM; P = .007) expression were significantly decreased. Retinoic X receptor– α expression tended to be increased by TO (171.9 ± 6.0 TO vs 155.4 ± 6.7 SHAM; P = .06). Conclusions Short-term TO late in gestation induces rapid lung growth. Surfactant protein–mRNA and protein expression are not significantly altered. Thyroid transcription factor 1 and Hoxb5 are down-regulated by TO, suggesting that duration and timing of occlusion are important in balancing the effects of TO on lung growth vs lung maturation.