Stem cell factor improves lung recovery in rats following neonatal hyperoxia-induced lung injury.
Stem cell factor improves lung recovery in rats following neonatal hyperoxia-induced lung injury.
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DOI：
10.1038/pr.2013.165
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发表时间：
2013-12
影响因子：
3.6
通讯作者：
Young KC
中科院分区：
文献类型：
--
作者：
Miranda LF;Rodrigues CO;Ramachandran S;Torres E;Huang J;Klim J;Hehre D;McNiece I;Hare JM;Suguihara CY;Young KC
干细胞因子（SCF）及其受体c-kit是血管生成的调节因子。新生儿高氧肺损伤（HILI）的特点是血管生成障碍。本研究的目的是确定外源性SCF是否通过改善血管生成来改善新生儿HILI的恢复。新生大鼠从出生后第2天（P）至第15天被分配到常氧（RA：20.9%O2）或高氧（90%O2）组，从P15至P21每天注射SCF 100 µg/kg或安慰剂（PL）。在P28进行肺形态测量。基质胶法测定SCF处理的高氧暴露的肺微血管内皮细胞（HPMEC）中的毛细血管形成。与RA相比，高氧PL幼鼠肺泡化和肺血管密度降低，这与右心室收缩压（RVSP）升高、右心室肥大和血管重塑有关。相比之下，SCF治疗的高氧幼仔血管生成增加，肺泡化改善，肺动脉高压减弱，如RVSP降低，右心室肥大和血管重塑所证明的。此外，在体外模型中，SCF增加了高氧暴露的HPMEC中的毛细血管形成。外源性SCF通过促进新生血管形成恢复新生大鼠HILI的肺泡和血管结构。这些发现为治疗以血管生成障碍为特征的肺部疾病提供了一种新的策略。
Stem cell factor (SCF) and its receptor, c-kit, are modulators of angiogenesis. Neonatal hyperoxia-induced lung injury (HILI) is characterized by disordered angiogenesis. The objective of this study was to determine whether exogenous SCF improves recovery from neonatal HILI by improving angiogenesis. Newborn rats assigned to normoxia (RA: 20.9% O2) or hyperoxia (90% O2) from postnatal day (P) 2 to 15, received daily injections of SCF 100 µg/kg or placebo (PL) from P15 to P21. Lung morphometry was performed at P28. Capillary tube formation in SCF-treated hyperoxia-exposed pulmonary microvascular endothelial cells (HPMECs) was determined by Matrigel assay. As compared with RA, hyperoxic-PL pups had decrease in alveolarization and in lung vascular density, and this was associated with increased right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and vascular remodeling. In contrast, SCF-treated hyperoxic pups had increased angiogenesis, improved alveolarization, and attenuation of pulmonary hypertension as evidenced by decreased RVSP, right ventricular hypertrophy, and vascular remodeling. Moreover, in an in vitro model, SCF increased capillary tube formation in hyperoxia-exposed HPMECs. Exogenous SCF restores alveolar and vascular structure in neonatal rats with HILI by promoting neoangiogenesis. These findings suggest a new strategy to treat lung diseases characterized by dysangiogenesis.