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The IGF-I/IGF-R1 Pathway Regulates Postnatal Lung Growth and Is a Nonspecific Regulator of Alveologenesis in the Neonatal Rat

Jun Li, Azhar Masood, Man Yi, Mandy Lau, Rosetta Belcastro, Julijana Ivanovska, Robert P Jankov, A Keith Tanswell

Am J Physiol Lung Cell Mol Physiol. 2013 May 1;304(9):L626-37.

PMID: 23457189

Abstract:

IGF-I, IGF-II, and the IGF-I receptor are widely distributed throughout the neonatal rat lung on days 4, 7, 10, and 14 of life, with a similar abundance at each of these time points. Injection of 20 μg/g of a truncated soluble IGF-I receptor on days 2 and 5 of life, to decoy ligand away from the endogenous IGF-I receptor, reduced lung weight and lung-to-body weight ratio, reduced lung tissue fraction, and impaired alveolar formation, as assessed by secondary crest formation and mean linear intercepts on day 7 of life. Lung procollagen I content and elastin fiber density were also reduced. Injection of 100 μg/day of neutralizing anti-IGF-I, to prevent IGF-I from binding to the IGF-I receptor, on days 3, 4, and 5 of life reduced tissue fraction and elastin fiber density and impaired alveolar formation on day 6 of life. Both interventions reduced total lung cell and secondary crest cell DNA synthesis and small vessel counts per unit area, but these effects were lost after normalization to the reduced tissue fraction. These findings are consistent with a role for IGF-I binding to the IGF-I receptor in postnatal lung growth and on alveologenesis through a nonspecific positive effect on DNA synthesis. Injection of 100 μg/day of neutralizing anti-IGF-II, to prevent IGF-II from binding to the IGF-I receptor, on days 3, 4, and 5 of life had no effect on total lung cell DNA synthesis per unit area on day 6 of life, and a role for IGF-II in postnatal alveologenesis was not further pursued.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR4248159 IGF-I from rat IGF-I from rat Price
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