The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
The circadian clock regulates rhythmic activation of the NRF2/glutathione-mediated antioxidant defense pathway to modulate pulmonary fibrosis
Open accessAbstract
The disruption of the NRF2 (nuclear factor erythroid-derived 2-like 2)/glutathione-mediated antioxidant defense pathway is a critical step in the pathogenesis of several chronic pulmonary diseases and cancer. While the mechanism of NRF2 activation upon oxidative stress has been widely investigated, little is known about the endogenous signals that regulate the NRF2 pathway in lung physiology and pathology. Here we show that an E-box-mediated circadian rhythm of NRF2 protein is essential in regulating the rhythmic expression of antioxidant genes involved in glutathione redox homeostasis in the mouse lung. Using an in vivo bleomycin-induced lung fibrosis model, we reveal a clock “gated” pulmonary response to oxidative injury, with a more severe fibrotic effect when bleomycin was applied at a circadian nadir in NRF2 levels. Timed administration of sulforaphane, an NRF2 activator, significantly blocked this phenotype. Moreover, in the lungs of the arrhythmic Clock Δ19 mice, the levels of NRF2 and the reduced glutathione are constitutively low, associated with increased protein oxidative damage and a spontaneous fibrotic-like pulmonary phenotype. Our findings reveal a pivotal role for the circadian control of the NRF2/glutathione pathway in combating oxidative/fibrotic lung damage, which might prompt new chronotherapeutic strategies for the treatment of human lung diseases, including idiopathic pulmonary fibrosis.
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1 retracted
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RetractedCoordination of circadian timing in mammals
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Coordinated Transcription of Key Pathways in the Mouse by the Circadian Clock
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Self-citationSimple method of estimating severity of pulmonary fibrosis on a numerical scale.
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Mutagenesis and Mapping of a Mouse Gene, Clock , Essential for Circadian Behavior
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NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential
Xie, N., Zhang, L., Gao, W., Huang, C., Huber, P. E., Zhou, X., Li, C., Shen, G., & Zou, B. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00311-7 · Cited by 1,052
Circadian Rhythm Disruption Promotes Lung Tumorigenesis
Papagiannakopoulos, T., Bauer, M. R., Davidson, S. M., Heimann, M., Subbaraj, L., Bhutkar, A., Bartlebaugh, J., Vander Heiden, M. G., & Jacks, T. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.07.001 · Cited by 557
“Metabolic reprograming of circadian mutant lung cancer cells Circadian rhythms are known to control a number of metabolic processes, including oxidative phosphorylation (Peek et al., 2013), redox homeostasis (Pekovic-Vaughan et al., 2014) and lipid metabolism (Grimaldi et al., 2010).”
Macrophages and Iron Metabolism
Soares, M. P., & Hamza, I. (2016) · Immunity · doi:10.1016/j.immuni.2016.02.016 · Cited by 401
Circadian clock protein BMAL1 regulates IL-1β in macrophages via NRF2
Early, J. O., Menon, D., Wyse, C. A., Cervantes-Silva, M. P., Zaslona, Z., Carroll, R. G., Palsson-McDermott, E. M., Angiari, S., Ryan, D. G., Corcoran, S. E., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1800431115 · Cited by 389
The mammalian circadian clock and its entrainment by stress and exercise
Tahara, Y., Aoyama, S., & Shibata, S. (2017) · The Journal of Physiological Sciences · doi:10.1007/s12576-016-0450-7 · Cited by 198
Metadata
- Authors
- Pekovic-Vaughan, V., Gibbs, J., Yoshitane, H., Yang, N., Pathiranage, D., Guo, B., Sagami, A., Taguchi, K., Bechtold, D., Loudon, A., Yamamoto, M., Chan, J., van der Horst, G. T. J., Fukada, Y., & Meng, Q.-J.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2014-03-15
- Volume
- 28
- Issue
- 6
- Pages
- 548-560
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2052720016
- Cited by
- 323
- References
- 56
- Type
- posted content
- Language
- en
- Open access
- diamond
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- The paper
- Pekovic-Vaughan, V., Gibbs, J., Yoshitane, H., Yang, N., Pathiranage, D., Guo, B., Sagami, A., Taguchi, K., Bechtold, D., Loudon, A., Yamamoto, M., Chan, J., van der Horst, G. T. J., Fukada, Y., & Meng, Q.-J. (2014). The circadian clock regulates rhythmic activation of the NRF2/glutathione-mediated antioxidant defense pathway to modulate pulmonary fibrosis. Genes & Development. https://doi.org/10.1101/gad.237081.113
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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