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

doi:10.1186/1465-9921-6-31

Respiratory Research

Volume 6

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Ahamed K
Epaud R
Holzenberger M
Bonora M
Flejou JF
Puard J
Clement A
Henrion-Caude A

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Epaud R
Holzenberger M
Bonora M
Flejou JF
Puard J
Clement A
Henrion-Caude A
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Research

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

Karmene Ahamed¹^* , Ralph Epaud¹^* , Martin Holzenberger² , Monique Bonora¹ , Jean-François Flejou³ , Julien Puard¹ , Annick Clement¹ and Alexandra Henrion-Caude¹

¹INSERM U719, Hospital Saint-Antoine, 75012 Paris, France

²INSERM U515, Hospital Saint-Antoine, 75012 Paris, France

³Department of Pathology, Hospital Saint-Antoine, 75012 Paris, France

author email corresponding author email* Contributed equally

Respiratory Research 2005, 6:31doi:10.1186/1465-9921-6-31


Published:	8 April 2005

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-1r^neo) and a knockout (Igf-1r^-) receptor allele. These IGF-1R^neo/-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-1R^neo/-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-1R^neo/-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-1R^neo/-mice.

Conclusion

Together, these data demonstrate that a decrease in IGF-1R signaling in mice protects against oxidant-induced lung injury.