Peri A, Dubin N H, Dhanireddy R, Mukherjee A B
Section on Developmental Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1830, USA.
J Clin Invest. 1995 Jul;96(1):343-53. doi: 10.1172/JCI118040.
Uteroglobin (UG) gene encodes a cytokine-like, multifunctional, antiinflammatory protein, with potent phospholipase A2-inhibitory activity. It has been suggested that during implantation this protein protects the embryos from maternal immunological assault, facilitates the maintenance of quiescence in the uterus throughout pregnancy, prevents the onset of premature labor, and helps maintain an inflammation-free respiratory organ. This latter function of UG is suggested to be accomplished by preventing hydrolysis of surfactant phospholipids by a lung-specific phospholipase A2. Using reverse transcription polymerase chain reaction, in situ hybridization, immunofluorescence, and radioimmunoassay, we studied UG gene expression in the rabbit uterus throughout gestation and in the fetal lung. Here, we report that: (a) contrary to previous reports, UG gene expression in the rabbit uterus occurs throughout gestation with a precipitous decline just before parturition; (b) this gene expression is dramatically increased in the fetal lung with increasing gestational age; and (c) while there is an inverse relationship between the levels of UG, PGE2, and PGF2 alpha, a positive correlation was found in that of UG and leukotriene C4 in the fetal lung. Our results raise the possibility that dysregulation of UG gene expression, at least in part, may contribute to the onset of premature labor and the development of inflammatory lung disease in premature neonates.
子宫珠蛋白(UG)基因编码一种细胞因子样的多功能抗炎蛋白,具有强大的磷脂酶A2抑制活性。有人提出,在着床期间,这种蛋白可保护胚胎免受母体免疫攻击,有助于整个孕期子宫维持静息状态,防止早产的发生,并有助于维持呼吸器官无炎症状态。UG的后一种功能被认为是通过阻止肺特异性磷脂酶A2水解表面活性物质磷脂来实现的。我们使用逆转录聚合酶链反应、原位杂交、免疫荧光和放射免疫测定法,研究了整个妊娠期兔子宫和胎儿肺中UG基因的表达。在此,我们报告:(a)与先前的报道相反,兔子宫中UG基因的表达在整个妊娠期均有发生,在分娩前急剧下降;(b)随着胎龄增加,该基因在胎儿肺中的表达显著增加;(c)虽然UG、前列腺素E2和前列腺素F2α水平之间呈负相关,但在胎儿肺中UG与白三烯C4水平呈正相关。我们的结果提出了一种可能性,即UG基因表达失调至少部分可能导致早产的发生以及早产儿炎性肺病的发展。