Noblesse Oblige: NRF2 Functions in the Airways
Noblesse Oblige: NRF2 Functions in the Airways
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DOI：
10.1165/rcmb.2014-0116ps
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发表时间：
2014-05-01
影响因子：
6.4
通讯作者：
Kleeberger, Steven R.
中科院分区：
文献类型：
--
作者：
Cho, Hye-Youn;Kleeberger, Steven R.
转录因子核因子（NF）、红细胞衍生2相关因子2 （NRF2）是近20年前发现的。从那时起，已有4000多篇关于NRF2在不同生物系统中的功能的论文发表，它被发现是抗氧化和防御基因的关键调节剂，其启动子中含有抗氧化反应元件。NRF2在保护高度氧化微环境下的细胞和组织方面尤其重要，包括与外部环境接触并暴露于污染物和其他氧化应激源的气道。使用靶向缺失Nrf2的小鼠，该转录因子在许多模型疾病中具有保护作用，包括急性肺损伤、肺气肿、过敏和哮喘、肺纤维化和呼吸道合胞病毒病。最近的研究还发现，小鼠Nrf2在肺发育和保护新生儿肺损伤中起重要作用。此外，已知人类NRF2的功能多态性与疾病严重程度相关，表明其具有潜在的重要保护功能。然而，NRF2的功能也有“阴暗面”，因为它已经被发现可以促进肺部和其他一些组织的晚期癌变。NRF2诱导剂，如植物化学异thyocyanates和合成三萜，已被发现并用于氧化诱导肺部疾病的模型系统中，数据表明其具有临床干预的潜力。未来对NRF2的研究将进一步深入了解其对气道正常和病理生理状况的贡献，以及防止氧化性呼吸疾病的替代治疗策略。
The transcription factor, nuclear factor (NF), erythroid-derived 2-related factor 2 (NRF2), was discovered nearly 2 decades ago. Since then, over 4,000 papers have been published on NRF2 function in diverse biological systems, and it has been found to be a critical regulator of antioxidant and defense genes with antioxidant response elements in their promoters. NRF2 is particularly important in protecting cells and tissues under highly oxidative microenvironments, including the airways that interface with the external environment and are exposed to pollutants and other oxidant stressors. Using mice with targeted deletion of Nrf2, a protective role for this transcription factor has been determined in many model diseases, including acute lung injury, emphysema, allergy and asthma, pulmonary fibrosis, and respiratory syncytial virus disease. Recent studies have also found that murine Nrf2 is important in lung development and protection against neonatal lung injury. Moreover, functional polymorphisms in human NRF2 have been known to associate with disease severity, indicating a potentially important protective function. However, there is also a "dark side" to NRF2 function, as it has been found to enhance advanced stages of carcinogenesis in the lung and some other tissues. NRF2 inducers such as phytochemical isothyocyanates and synthetic triterpenoids, have been discovered and used in model systems of oxidant-induced lung diseases, and data suggest a potential for clinical interventions. Future investigations of NRF2 should yield further insight into its contribution to normal and pathophysiological conditions in the airways, and alternative treatment strategies to protect against oxidative respiratory disease.