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Deficiency in type 1 insulin-like growth factor receptor in mice protects against oxygen-induced lung injury.

Abstract : BACKGROUND: Cellular responses to aging and oxidative stress are regulated by type 1 insulin-like growth factor receptor (IGF-1R). Oxidant injury, which is implicated in the pathophysiology of a number of respiratory diseases, acutely upregulates IGF-1R expression in the lung. This led us to suspect that reduction of IGF-1R levels in lung tissue could prevent deleterious effects of oxygen exposure. METHODS: Since IGF-1R null mutant mice die at birth from respiratory failure, we generated compound heterozygous mice harboring a hypomorphic (Igf-1rneo) and a knockout (Igf-1r-) receptor allele. These IGF-1Rneo/- mice, strongly deficient in IGF-1R, were subjected to hyperoxia and analyzed for survival time, ventilatory control, pulmonary histopathology, morphometry, lung edema and vascular permeability. RESULTS: Strikingly, after 72 h of exposure to 90% O2, IGF-1Rneo/- mice had a significantly better survival rate during recovery than IGF-1R+/+ mice (77% versus 53%, P < 0.05). The pulmonary injury was consistently, and significantly, milder in IGF-1Rneo/- mice which developed conspicuously less edema and vascular extravasation than controls. Also, hyperoxia-induced abnormal pattern of breathing which precipitated respiratory failure was elicited less frequently in the IGF-1Rneo/- mice. CONCLUSION: Together, these data demonstrate that a decrease in IGF-1R signaling in mice protects against oxidant-induced lung injury.
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Submitted on : Tuesday, September 5, 2006 - 4:19:18 PM
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Karmene Ahamed, Ralph Epaud, Martin Holzenberger, Monique Bonora, Jean-François Flejou, et al.. Deficiency in type 1 insulin-like growth factor receptor in mice protects against oxygen-induced lung injury.. Respiratory Research, BioMed Central, 2005, 6, pp.31. ⟨10.1186/1465-9921-6-31⟩. ⟨inserm-00090937⟩



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