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Differential effects of exogenous IGF-1 administration on young adult and geriatric mice following pneumonectomy

Yasa, J., Huang, W., Liu, L., Engineer, D., Prele, C., Laurent, G., Lucas, M. and Lucas, A. (2018) Differential effects of exogenous IGF-1 administration on young adult and geriatric mice following pneumonectomy. Respirology, 23 (S1). p. 184.

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Introduction/Aim: The murine unilateral pneumonectomy (PNX) model induces growth of new alveolar tissue in the remaining lung, increasing lung mass and volume 14d after surgery. This compensatory lung growth response declines as mammal’s age. We aimed to determine whether infusion of Insulin-like Growth Factor (IGF)-1 could enhance lung growth in young adult mice and very old mice following PNX.

Methods: Groups of 5 – 8, female C57BL6/J mice aged 12 weeks or 23 months, received both a left sided PNX and also the subcutaneous insertion of an osmotic pump, delivering either rhIGF-1 or PBS. To determine changes in lung volume, mice were imaged by micro-Computerised Tomography at days 4,7,14 and 21 and then sacrificed, the right lung inflated, embedded and examined by immunohistochemistry.

Results: Following PNX in 12 week old mice, there is a rapid increase in lung volume which approaches pre-operative volumes by d4. IGF-1 supplementation following PNX in 12 week old mice significantly increased Ki67+ and Ki67/SpC+ lung cell numbers, at day 21 post-surgery, but did not affect magnitude of lung volume change compared to PBS treated mice. In contrast in old mice, there was a much less pronounced increase in total lung volume of the right lung following surgery. IGF-1 supplementation following PNX surgery significantly increased the volume of air in the lungs compared to PBS treated old mice, but not to the level of preoperative lung volumes and had no effect on tissue content or cell proliferation.

Conclusion: Exogenous IGF-1 treatment does not accelerate or increase lung growth in 12 week old mice or induce lung growth in old mice, following PNX. IGF-1 treatment did significantly increase the lung volume and reduce the lung density in old mice.

Grant Support: This work was supported by 2 grants awarded by the Charles Gairdner Osborne Park Health Care Group and by a UWA/- Helmholtz Institute/UCL Seed Funding Grant.

Item Type: Journal Article
Murdoch Affiliation(s): School of Veterinary and Life Sciences
Publisher: Wiley-Blackwell
Copyright: © 2018 Asian Pacific Society of Respirology
Other Information: Special Issue: The Australia & New Zealand Society of Respiratory Science and The Thoracic Society of Australia and New Zealand (ANZSRS/TSANZ) Annual Scientific Meeting, Adelaide, Australia, 23–27 March 2018
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