INSULIN-LIKE GROWTH-FACTOR-I GENE-EXPRESSION IN 3 MODELS OF ACCELERATED LUNG GROWTH

Background/Purpose: We have learned previously that in utero tracheal ligation reverses the structural and physiological effects of surgical ly created congenital diaphragmatic hernia. In addition, we have disco vered that postnatal lung growth similarly can be accelerated using li quid-based airway distension with perfluorocarbon. Another model of ac celerated lung growth is that of compensatory growth seen after neonat al pneumonectomy. In all of these models, growth has occurred because of an increase in alveolar number rather than enlargement of preexisti ng alveoli. However, the molecular mechanisms underlying these process es remain unknown. The purpose of th is study was to determine if gene expression could be altered by changes in physical forces in the pren atal and postnatal lung. Methods: The three models of accelerated lung growth studied we re the following: (1) The prenatal group, consisted of fetal lambs (n = 12) that underwent the surgical creation of a lef t diaphragmatic hernia at 90 days' gestation. Six of these animals als o underwent simultaneous tracheal ligation. (2) The PFC group consiste d of five neonatal animals that underwent isolation of the superior se gment of the right upper lobe, with intrabronchial distension with per fluorocarbon to 7 to 10 mm Hg pressure for a 3-week period. (3) The po stpneumonectomy group consisted of four neonatal animals that underwen t left pneumonectomy. In the fetal study, lungs were retrieved at term (130 days), and in the postnatal study, lungs were retrieved 3 weeks after initial intervention. In all cases, RNA was extracted from snap- frozen lung samples and Northern blot analysis performed. Results: Ins ulinlike growth factor-I, insulinlike growth factor-II, and vascular e ndothelial growth factor gene expression were analyzed by densitometry . Insulinlike growth factor-I gene expression was found to be decrease d in association with experimental diaphragmatic hernia (P = .005), bu t restored to normal with tracheal ligation. Insulinlike growth factor -I gene expression was significantly increased in both postnatal model s of accelerated lung growth (P = .022, P = .016). No significant diff erences were found in insulinlike growth factor-II or vascular endothe lial growth factor gene expression. Conclusions: The authors conclude from these preliminary data that (1) insulin like growth factor-I gene expression is reduced in experimental fetal diaphragmatic hernia and restored to normal by tracheal ligation, and (2) insulinlike growth fa ctor-I gene expression is increased in both the liquid-based airway di stension and postpneumonectomy models of accelerated postnatal lung gr owth. The authors speculate that all of these manipulations exploit a natural pathway essential for normal lung growth. J Pediatr Surg 33:10 57-1061. Copyright (C) 1998 by W.B. Saunders Company.