Division of Neonatology, University of Utah, Salt Lake City, Utah, USA.
Physiol Genomics. 2011 May 13;43(9):499-505. doi: 10.1152/physiolgenomics.00183.2010. Epub 2011 Mar 1.
Complications of intrauterine growth restriction (IUGR) include increased pulmonary morbidities and impaired alveolar development. Normal alveolar development depends upon elastin expression and processing, as well as the formation and deposition of elastic fibers. This is true of the human and rat. In this study, we hypothesized that uteroplacental insufficiency (UPI)-induced IUGR decreases mRNA levels of elastin and genes required for elastin fiber synthesis and assembly, at birth (prealveolarization) and postnatal day 7 (midalveolarization) in the rat. We further hypothesized that this would be accompanied by reduced elastic fiber deposition and increased static compliance at postnatal day 21 (mature lung). We used a well characterized rat model of IUGR to test these hypotheses. IUGR decreases mRNA transcript levels of genes essential for elastic fiber formation, including elastin, at birth and day 7. In the day 21 lung, IUGR decreases elastic fiber deposition and increases static lung compliance. We conclude that IUGR decreases mRNA transcript levels of elastic fiber synthesis genes, before and during alveolarization leading to a reduced elastic fiber density and increased static lung compliance in the mature lung. We speculate that the mechanism by which IUGR predisposes to pulmonary disease may be via decreased lung elastic fiber deposition.
宫内生长受限(IUGR)的并发症包括肺部疾病增多和肺泡发育受损。正常的肺泡发育依赖于弹性蛋白的表达和加工,以及弹性纤维的形成和沉积。这在人和大鼠中都是如此。在这项研究中,我们假设,胎盘功能不全(UPI)引起的 IUGR 在出生时(肺泡前期)和出生后第 7 天(中肺泡期)降低大鼠的弹性蛋白和弹性纤维合成和组装所需基因的 mRNA 水平。我们进一步假设,这将伴随着出生后第 21 天(成熟肺)弹性纤维沉积减少和静态顺应性增加。我们使用一种经过充分验证的大鼠 IUGR 模型来检验这些假设。IUGR 在出生和第 7 天降低了弹性纤维形成所需基因的 mRNA 转录水平,包括弹性蛋白。在第 21 天的肺中,IUGR 减少了弹性纤维的沉积并增加了静态肺顺应性。我们得出结论,IUGR 在肺泡化之前和期间降低了弹性纤维合成基因的 mRNA 转录水平,导致成熟肺中的弹性纤维密度降低和静态肺顺应性增加。我们推测,IUGR 易患肺部疾病的机制可能是通过减少肺弹性纤维沉积。