The IGF-I/IGF-R1 pathway regulates postnatal lung growth and is a nonspecific regulator of alveologenesis in the neonatal rat
The IGF-I/IGF-R1 pathway regulates postnatal lung growth and is a nonspecific regulator of alveologenesis in the neonatal rat
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DOI：
10.1152/ajplung.00198.2012
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发表时间：
2013-05-01
影响因子：
4.9
通讯作者：
Tanswell, A. Keith
中科院分区：
文献类型：
--
作者：
Li, Jun;Masood, Azhar;Tanswell, A. Keith
IGF-I、IGF-II和IGF-I受体在出生后的第4,7,10和14天广泛分布于新生大鼠的肺部，在这些时间点上的丰度相似。在出生后第2天和第5天注射20 μ g/g截断的可溶性IGF-I受体，以诱离内源性IGF-I受体的配体，降低肺重量和肺体重比，减少肺组织分数，并损害肺泡形成，这是由出生后第7天的次峰形成和平均线性截距来评估的。肺I型前胶原含量和弹性蛋白纤维密度也降低。在出生第3、4、5天注射100 μ g/天的中和性抗IGF-I，以阻止IGF-I与IGF-I受体结合，在出生第6天组织分数和弹性蛋白纤维密度降低，肺泡形成受损。两种干预措施都减少了肺细胞和次级嵴细胞的DNA合成总量和单位面积的小血管计数，但这些影响在归一化后就消失了。这些发现与IGF-I结合IGF-I受体在出生后肺生长和肺泡形成中的作用是一致的，其作用是通过对DNA合成的非特异性积极作用。在出生后第3,4,5天注射100 μ g/天的中和抗IGF-II，以防止IGF-II与IGF-I受体结合，对出生后第6天单位面积的肺细胞DNA合成总量没有影响，并且IGF-II在出生后肺泡形成中的作用没有进一步的研究。
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 mu g/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 mu g/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 mu g/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.