Runt-Related Transcription Factor 1 Regulates LPS-Induced Acute Lung Injury via NF-κB Signaling
Runt-Related Transcription Factor 1 Regulates LPS-Induced Acute Lung Injury via NF-κB Signaling
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DOI：
10.1165/rcmb.2016-0319oc
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发表时间：
2017-08-01
影响因子：
6.4
通讯作者：
Luo, Fengming
中科院分区：
文献类型：
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作者：
Tang, Xiaoju;Sun, Ling;Luo, Fengming
Runt-related transcription factor 1（RUNX 1）是一种在多种器官中表达的转录因子，在胚胎发育和造血过程中起重要作用。尽管RUNX 1在肺组织中高度表达，但其在肺功能和体内平衡中的作用尚不清楚。我们试图评估RUNX 1在LPS激发后肺发育和炎症中的作用。在发育和出生后的肺中评估RUNX 1的表达。RUNX 1在肺上皮细胞中有条件地缺失。在发育中和出生后的肺中评价肺成熟，并在LPS攻击后在成年小鼠中研究肺部炎症。在体外评估了RUNX 1与通过NF-κ B-IkB激酶β的炎症信号传导之间的相互作用。RUNX 1在发育和出生后肺的间充质和上皮隔室中表达。RUNX 1基因从产生Runx 1（Delta/Delta）小鼠的呼吸道上皮细胞中有效地删除。尽管肺成熟延迟，Runx 1（Delta/Delta）小鼠出生后存活，随后肺的生长和成熟正常进行。在Runx 1缺失小鼠肺部LPS暴露后，观察到呼吸窘迫、炎症和促炎细胞因子增加。RUNX 1缺失与呼吸道上皮细胞中NF-κ B B的活化相关。在体外研究中，RUNX 1是通过抑制Ik B激酶β抑制NF-κ B信号传导途径所必需的。RUNX 1在LPS诱导的肺损伤后的炎症反应中起关键作用。
Runt-related transcription factor 1 (RUNX1), a transcription factor expressed in multiple organs, plays important roles in embryonic development and hematopoiesis. Although RUNX1 is highly expressed in pulmonary tissues, its roles in lung function and homeostasis are unknown. We sought to assess the role of RUNX1 in lung development and inflammation after LPS challenge. Expression of RUNX1 was assessed in the developing and postnatal lung. RUNX1 was conditionally deleted in pulmonary epithelial cells. Pulmonary maturation was evaluated in the developing and postnatal lung, and lung inflammation was investigated in adult mice after LPS challenge. Interactions between RUNX1 and inflammatory signaling via NF-kappa B-IkB kinase beta were assessed in vitro. RUNX1 was expressed in both mesenchymal and epithelial compartments of the developing and postnatal lung. The RUNX1 gene was efficiently deleted from respiratory epithelial cells producing Runx1(Delta/Delta) mice. Although lung maturation was delayed, Runx1(Delta/Delta) mice survived postnatally and subsequent growth and maturation of the lung proceeded normally. Increased respiratory distress, inflammation, and proinflammatory cytokines were observed in the Runx1-deleted mice after pulmonary LPS exposure. RUNX1 deletion was associated with the activation of NF-kappa B in respiratory epithelial cells. RUNX1 was required for the suppression of NF-kappa B signaling pathway via inhibition of IkB kinase beta in in vitro studies. RUNX1 plays a critical role in the lung inflammation after LPS-induced injury.