Key developmental regulators change during hyperoxia-induced injury and recovery in adult mouse lung
Key developmental regulators change during hyperoxia-induced injury and recovery in adult mouse lung
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DOI：
10.1002/jcb.21142
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发表时间：
2007-04-15
影响因子：
4
通讯作者：
Williams, Mary C.
中科院分区：
文献类型：
--
作者：
Pogach, Melanie S.;Cao, Yuxia;Williams, Mary C.
发育重要的基因最近被链接到新生儿和成年动物的几个器官，包括肝脏，皮肤，前列腺和肌肉组织的组织再生和上皮细胞修复。我们假设发育重要的基因在成年小鼠的肺损伤修复中发挥作用。虽然有相当多的信息已知这些过程，具体的分子途径，介导损伤和调节组织修复没有完全阐明。使用高氧损伤模型来研究肺损伤和组织修复的这些机制，我们基于它们在肺发育和器官发生中的已知或推定作用选择了以下基因：TTF-1、FGF 9、FGF 10、BMP 4、PDGF-A、VEGF、Ptc、Shh、Sca-1、BCRP、CD 45和细胞周期蛋白-D2。我们的研究结果表明，几个发育重要的基因（Sca-1，Shh，PDCF-A，VEGF，BCRP，CD 45，BMP 4和Cyclin-D2）在小鼠高氧损伤和常氧恢复过程中发生变化，表明成年肺可能重新激活组织修复的关键发育调控途径。一个基因（TTF-1）的mRNA在高氧期间不变，在恢复期后期上调。这些新的发现提供了基础，用于测试在转基因动物中损伤后肺修复的功效，以表达或表达单个分子。J.细胞。100：1415-1429，2007.
Developmentally important genes have recently been linked to tissue regeneration and epithelial cell repair in neonatal and adult animals in several organs, including liver, skin, prostate, and musculature. We hypothesized that developmentally important genes play roles in lung injury repair in adult mice. Although there is considerable information known about these processes, the specific molecular pathways that mediate injury and regulate tissue repair are not fully elucidated. Using a hyperoxic injury model to study these mechanisms of lung injury and tissue repair, we selected the following genes based upon their known or putative roles in lung development and organogenesis: TTF-1, FGF9, FGF10, BMP4, PDGF-A, VEGF, Ptc, Shh, Sca-1, BCRP, CD45, and Cyclin-D2. Our findings demonstrate that several developmentally important genes (Sca-1, Shh, PDCF-A, VEGF, BCRP, CD45, BMP4, and Cyclin-D2) change during hyperoxic injury and normoxic recovery in mice, suggesting that adult lung may reactivate key developmental regulatory pathways for tissue repair. The mRNA for one gene (TTF-1), unchanged during hyperoxia, was upregulated late in recovery phase. These novel findings provide the basis for testing the efficacy of post-injury lung repair in animals genetically modified to inactivate or express individual molecules. J. Cell. Biochem. 100: 1415-1429, 2007.