Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Rochester Medical Center, Rochester, NY, USA.
Free Radic Biol Med. 2018 May 1;119:121-128. doi: 10.1016/j.freeradbiomed.2017.10.383. Epub 2017 Oct 31.
At the cellular level, circadian timing is maintained by the molecular clock, a family of interacting clock gene transcription factors, nuclear receptors and kinases called clock genes. Daily rhythms in pulmonary function are dictated by the circadian timing system, including rhythmic susceptibility to the harmful effects of airborne pollutants, exacerbations in patients with chronic airway disease and the immune-inflammatory response to infection. Further, evidence strongly suggests that the circadian molecular clock has a robust reciprocal interaction with redox signaling and plays a considerable role in the response to oxidative/carbonyl stress. Disruption of the circadian timing system, particularly in airway cells, impairs pulmonary rhythms and lung function, enhances oxidative stress due to airway inhaled pollutants like cigarette smoke and airborne particulate matter and leads to enhanced inflammosenescence, inflammasome activation, DNA damage and fibrosis. Herein, we briefly review recent evidence supporting the role of the lung molecular clock and redox signaling in regulating inflammation, oxidative stress, and DNA damage responses in lung diseases and their exacerbations. We further describe the potential for clock genes as novel biomarkers and therapeutic targets for the treatment of chronic lung diseases.
在细胞水平上，生物钟由分子钟维持，分子钟是一组相互作用的时钟基因转录因子、核受体和激酶，称为时钟基因。肺功能的昼夜节律由生物钟系统决定，包括对空气传播污染物的有害影响的节律易感性、慢性气道疾病患者的恶化以及对感染的免疫炎症反应。此外，有强有力的证据表明，生物钟的昼夜节律分子与氧化还原信号之间存在强大的相互作用，并在对氧化/羰基应激的反应中发挥重要作用。生物钟系统的破坏，特别是在气道细胞中，会损害肺节律和肺功能，由于气道吸入的污染物如香烟烟雾和空气传播的颗粒物而增强氧化应激，并导致增强的炎症衰老、炎症小体激活、DNA 损伤和纤维化。在此，我们简要回顾了支持肺分子钟和氧化还原信号在调节肺部疾病及其恶化中的炎症、氧化应激和 DNA 损伤反应中的作用的最新证据。我们进一步描述了时钟基因作为治疗慢性肺部疾病的新型生物标志物和治疗靶点的潜力。
