Silencing hyperoxia-induced C/EBPα in neonatal mice improves lung architecture via enhanced proliferation of alveolar epithelial cells.
Silencing hyperoxia-induced C/EBPα in neonatal mice improves lung architecture via enhanced proliferation of alveolar epithelial cells.
复制标题
在新生小鼠中沉默高氧诱导的 C/EBPα 可通过增强肺泡上皮细胞的增殖来改善肺结构。
DOI：
10.1152/ajplung.00082.2011
复制
发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Dennery,PhyllisA
中科院分区：
文献类型：
--
作者：
Yang,Guang;Hinson,MauriceD;Bordner,JessicaE;Lin,QingS;Fernando,AmalP;La,Ping;Wright,ClydeJ;Dennery,PhyllisA
出生后肺的发育需要特定类型的细胞在精确的时间内增殖和分化，以促进适当的肺泡形成。高氧暴露可通过抑制细胞生长来破坏肺泡化；然而，这一过程是如何介导的还不完全清楚。转录因子CCAAT/增强子结合蛋白-α(C/EBPα)在肺组织中高表达，在许多组织中起细胞增殖和分化的作用。高氧72h后，新生小鼠肺组织中C/EBPα表达显著增强。C/EBPα蛋白表达增加，主要定位于肺泡II型细胞。在高氧暴露前经肺内注射C/EBPsiRNA沉默C/EBPsiRNA，可减少高氧后典型的I型细胞标志物的表达和分化，但不能挽救72h时肺组织的形态变化。然而，与高氧暴露的对照α相比，C/EBPsiRNA注射小鼠在室内空气中恢复2wk后，肺上皮细胞增殖增加，肺形态得到恢复。提示C/EBPα在肺损伤修复过程中是肺泡上皮细胞增殖和分化的重要调节因子。
Postnatal lung development requires proliferation and differentiation of specific cell types at precise times to promote proper alveolar formation. Hyperoxic exposure can disrupt alveolarization by inhibiting cell growth; however, it is not fully understood how this is mediated. The transcription factor CCAAT/enhancer binding protein-α (C/EBPα) is highly expressed in the lung and plays a role in cell proliferation and differentiation in many tissues. After 72 h of hyperoxia, C/EBPα expression was significantly enhanced in the lungs of newborn mice. The increased C/EBPα protein was predominantly located in alveolar type II cells. Silencing of C/EBPα with a transpulmonary injection of C/EBPα small interfering RNA (siRNA) prior to hyperoxic exposure reduced expression of markers of type I cell and differentiation typically observed after hyperoxia but did not rescue the altered lung morphology at 72 h. Nevertheless, when C/EBPα hyperoxia-exposed siRNA-injected mice were allowed to recover for 2 wk in room air, lung epithelial cell proliferation was increased and lung morphology was restored compared with hyperoxia-exposed control siRNA-injected mice. These data suggest that C/EBPα is an important regulator of postnatal alveolar epithelial cell proliferation and differentiation during injury and repair.