Alterations in lung expansion affect surfactant protein A, B, and C mRNA levels in fetal sheep
Alterations in lung expansion affect surfactant protein A, B, and C mRNA levels in fetal sheep
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DOI：
10.1152/ajplung.1999.276.2.l239
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发表时间：
1999-02-01
影响因子：
4.9
通讯作者：
Hooper, SB
中科院分区：
文献类型：
--
作者：
Lines, A;Nardo, L;Hooper, SB
胎儿气管阻塞是对胎儿肺部生长的有效刺激，并且有人建议该手术可用于治疗性地逆转患有肺发育不全的人类胎儿的肺部生长缺陷。然而，人们对肺扩张增加对肺发育其他方面的影响知之甚少。我们的目的是确定增加和减少肺扩张对绵羊胎肺中编码表面活性蛋白 (SP) A、SP-B 和 SP-C 的 mRNA 水平的影响。肺组织样本是从因气管阻塞导致肺扩张增加 2、4 或 10 天的胎儿中采集的。 SP-A、SP-B 和 SP-C 的 mRNA 水平：通过使用特定绵羊 cDNA 探针的 Northern 印迹分析来测定； SP-A蛋白水平通过蛋白质印迹分析测定。与年龄匹配（胎龄128天）的对照胎儿相比，气管阻塞第2天胎儿肺组织中SP-A、SP-B和SP-C mRNA水平显着降低，并在第4和10天持续降低。然而，气管阻塞第2天SP-A蛋白水平并未降低，第4天有降低趋势，第10天几乎检测不到。与气管阻塞相反，与年龄匹配的对照胎儿相比，7天的肺液体引流显着增加了胎儿肺组织中SP-C的mRNA水平，但没有增加SP-A的mRNA水平。我们的结果表明，胎儿气管阻塞引起的胎儿肺扩张增加，导致胎儿肺中 SP-A、SP-B 和 SP-C mRNA 水平同时大幅降低，以及 SP-A 蛋白水平降低。这些数据表明，胎儿肺中编码 SP 的基因表达对肺扩张程度有特异性反应。
Obstruction of the fetal trachea is a potent stimulus for fetal lung growth, and it has been suggested that this procedure may be used therapeutically to reverse lung growth deficits in human fetuses with lung hypoplasia. However little is known about the effects of increased lung expansion on other aspects of lung development. Our aim was to determine the effect of increased and decreased lung expansion on the mRNA levels encoding surfactant protein (SP) A, SP-B, and SP-C in ovine fetal lungs. Lung tissue samples were collected from fetuses exposed to 2, 4, or 10 days of increased lung expansion caused by tracheal obstruction. The mRNA levels for SP-A, SP-B, and SP-C: were determined by Northern blot analysis with specific ovine cDNA probes; SP-A protein levels were determined by Western blot analysis. Compared with age-matched (128-day gestational age) control fetuses, SP-A, SP-B, and SP-C mRNA levels in fetal lung tissue were significantly reduced at 2 days of tracheal obstruction and remained reduced at 4 and 10 days. However, SP-A protein levels were not reduced at 2 days of tracheal obstruction, tended to be reduced at 4 days, and were almost undetectable at 10 days. In contrast to tracheal obstruction, 7 days of lung liquid drainage significantly increased SP-C, but not SP-A, mRNA levels in fetal lung tissue compared with age-matched control fetuses. Our results demonstrate that increases in fetal lung expansion, induced by obstruction of the fetal trachea, cause large simultaneous reductions in SP-A, SP-B, and SP-C mRNA levels in the fetal lung as well as a decrease in SP-A protein levels, These data suggest that expression of the genes encoding SPs in the fetal lung are specifically responsive to the degree of lung expansion.