Department of Pediatrics, Yale University, New Haven, Connecticut, United States of America.
PLoS One. 2013 Apr 29;8(4):e60560. doi: 10.1371/journal.pone.0060560. Print 2013.
The role and mechanism of action of MIF in hyperoxia-induced acute lung injury (HALI) in the newborn lung are not known. We hypothesized that MIF is a critical regulatory molecule in HALI in the developing lung.
We studied newborn wild type (WT), MIF knockout (MIFKO), and MIF lung transgenic (MIFTG) mice in room air and hyperoxia exposure for 7 postnatal (PN) days. Lung morphometry was performed and mRNA and protein expression of vascular mediators were analyzed.
MIF mRNA and protein expression were significantly increased in WT lungs at PN7 of hyperoxia exposure. The pattern of expression of Angiopoietin 2 protein (in MIFKO>WT>MIFTG) was similar to the mortality pattern (MIFKO>WT>MIFTG) in hyperoxia at PN7. In room air, MIFKO and MIFTG had modest but significant increases in chord length, compared to WT. This was associated with decreased expression of Angiopoietin 1 and Tie 2 proteins in the MIFKO and MIFTG, as compared to the WT control lungs in room air. However, on hyperoxia exposure, while the chord length was increased from their respective room air controls, there were no differences between the 3 genotypes.
These data point to the potential roles of Angiopoietins 1, 2 and their receptor Tie2 in the MIF-regulated response in room air and upon hyperoxia exposure in the neonatal lung.
MIF 在新生肺高氧诱导的急性肺损伤（HALI）中的作用和作用机制尚不清楚。我们假设 MIF 是发育中肺 HALI 的关键调节分子。
我们在常氧和高氧暴露下研究了新生野生型（WT）、MIF 敲除（MIFKO）和 MIF 肺转基因（MIFTG）小鼠，共 7 天。进行肺形态计量学检查，并分析血管介质的 mRNA 和蛋白表达。
MIF 在高氧暴露的 WT 肺中在第 7 天的 mRNA 和蛋白表达显著增加。血管生成素 2 蛋白的表达模式（MIFKO>WT>MIFTG）与第 7 天高氧时的死亡率模式（MIFKO>WT>MIFTG）相似。在常氧下，MIFKO 和 MIFTG 与 WT 相比，有适度但显著增加的索长。这与 MIFKO 和 MIFTG 肺中血管生成素 1 和 Tie 2 蛋白的表达减少有关，与常氧下的 WT 对照肺相比。然而，在高氧暴露下，尽管索长与其各自的常氧对照相比有所增加，但 3 种基因型之间没有差异。
这些数据表明，血管生成素 1、2 及其受体 Tie2 在 MIF 调节的反应中具有潜在的作用，无论是在常氧下还是在新生肺的高氧暴露下。
