Soo Jia Yin, Orgeig Sandra, McGillick Erin Victoria, Zhang Song, McMillen I Caroline, Morrison Janna L
Early Origins of Adult Health Research Group, School of Pharmacy & Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, SA, Australia.
Molecular & Evolutionary Physiology of the Lung Laboratory, School of Pharmacy & Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, SA, Australia.
PLoS One. 2017 Sep 26;12(9):e0181185. doi: 10.1371/journal.pone.0181185. eCollection 2017.
Intrauterine growth restriction (IUGR) induced by placental restriction (PR) in the sheep negatively impacts lung and pulmonary surfactant development during fetal life. Using a sheep model of low birth weight (LBW), we found that there was an increase in mRNA expression of surfactant protein (SP)-A, -B and -C in the lung of LBW lambs but no difference in the protein expression of SP-A or -B. LBW also resulted in increased lysosome-associated membrane glycoprotein (LAMP)-3 mRNA expression, which may indicate an increase in either the density of type II Alveolar epithelial cells (AEC) or maturity of type II AECs. Although there was an increase in glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase (11βHSD)-1 mRNA expression in the lung of LBW lambs, we found no change in the protein expression of these factors, suggesting that the increase in SP mRNA expression is not mediated by increased GC signalling in the lung. The increase in SP mRNA expression may, in part, be mediated by persistent alterations in hypoxia signalling as there was an increase in lung HIF-2α mRNA expression in the LBW lamb. The changes in the hypoxia signalling pathway that persist within the lung after birth may be involved in maintaining SP production in the LBW lamb.
绵羊胎盘限制(PR)诱导的子宫内生长受限(IUGR)对胎儿期肺和肺表面活性物质的发育产生负面影响。使用低出生体重(LBW)绵羊模型,我们发现LBW羔羊肺中表面活性蛋白(SP)-A、-B和-C的mRNA表达增加,但SP-A或-B的蛋白表达无差异。LBW还导致溶酶体相关膜糖蛋白(LAMP)-3 mRNA表达增加,这可能表明II型肺泡上皮细胞(AEC)密度增加或II型AEC成熟度增加。尽管LBW羔羊肺中糖皮质激素受体(GR)和11β-羟基类固醇脱氢酶(11βHSD)-1的mRNA表达增加,但我们发现这些因子的蛋白表达没有变化,这表明SP mRNA表达的增加不是由肺中GC信号增加介导的。SP mRNA表达的增加可能部分是由缺氧信号的持续改变介导的,因为LBW羔羊肺中HIF-2α mRNA表达增加。出生后肺内持续存在的缺氧信号通路变化可能参与维持LBW羔羊的SP产生。