Circadian regulation of lung repair and regeneration.
Circadian regulation of lung repair and regeneration.
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DOI：
10.1172/jci.insight.164720
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发表时间：
2023-08-22
期刊：
影响因子：
8
通讯作者：
Sengupta, Shaon
中科院分区：
文献类型：
--
作者：
Naik, Amruta;Forrest, Kaitlyn M.;Paul, Oindrila;Issah, Yasmine;Valekunja, Utham K.;Tang, Soon Y.;Reddy, Akhilesh B.;Hennessy, Elizabeth J.;Brooks, Thomas G.;Chaudhry, Fatima;Babu, Apoorva;Morley, Michael;Zepp, Jarod A.;Grant, Gregory R.;Fitzgerald, Garret A.;Sehgal, Amita;Worthen, G. Scott;Frank, David B.;Morrisey, Edward E.;Sengupta, Shaon
最佳的肺修复和再生对于从包括甲型流感病毒（IAV）在内的病毒感染中恢复至关重要。我们先前已经证明，IAV引发的急性炎症和死亡率受昼夜节律控制。然而，尚不清楚昼夜节律钟的影响是否在急性结果之后仍然存在。在此，我们利用英国生物银行来证明不良的昼夜节律与下呼吸道感染的发病率之间存在关联，包括住院需求以及出院后的死亡率；即使在对常见的混杂因素进行调整后，这种关联仍然存在。此外，我们结合使用肺类器官检测、单细胞RNA测序以及在不同的生物钟紊乱模型中进行IAV感染，以研究昼夜节律钟在肺修复和再生中的作用。我们表明肺类器官具有功能性的昼夜节律钟，并且该钟的紊乱会损害再生能力。最后，我们发现昼夜节律钟通过不同的途径介导肺再生——在气管细胞中通过Wnt/β - 连环蛋白途径，在肺泡上皮细胞中通过白细胞介素 - 1β。我们推测，在肺修复和再生这一关键过程中加入昼夜节律维度将催生新的疗法并改善治疗结果。
Optimal lung repair and regeneration are essential for recovery from viral infections, including influenza A virus (IAV). We have previously demonstrated that acute inflammation and mortality induced by IAV is under circadian control. However, it is not known whether the influence of the circadian clock persists beyond the acute outcomes. Here, we utilize the UK Biobank to demonstrate an association between poor circadian rhythms and morbidity from lower respiratory tract infections, including the need for hospitalization and mortality after discharge; this persists even after adjusting for common confounding factors. Furthermore, we use a combination of lung organoid assays, single-cell RNA sequencing, and IAV infection in different models of clock disruption to investigate the role of the circadian clock in lung repair and regeneration. We show that lung organoids have a functional circadian clock and the disruption of this clock impairs regenerative capacity. Finally, we find that the circadian clock acts through distinct pathways in mediating lung regeneration — in tracheal cells via the Wnt/β-catenin pathway and through IL-1β in alveolar epithelial cells. We speculate that adding a circadian dimension to the critical process of lung repair and regeneration will lead to novel therapies and improve outcomes.
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影响因子：
82.9
作者：
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影响因子：
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作者：
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发表时间：
2018-09-04
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5.9
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