| Title: | Circadian regulation of lung repair and regeneration |
| Journal: | JCI Insight |
| Published: | 22 Aug 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37463053/ |
| DOI: | https://doi.org/10.1172/jci.insight.164720 |
| URL: | http://insight.jci.org/articles/view/164720/files/pdf |
Publication 9723
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
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.</p>
20 Authors
- Amruta Naik
- Kaitlyn M. Forrest
- Oindrila Paul
- Yasmine Issah
- Utham Kashyap Valekunja
- Soon Yew Tang
- Akhilesh B. Reddy
- Elizabeth J. Hennessy
- Thomas G. Brooks
- Fatima N. Chaudhry
- Apoorva Babu
- Michael P. Morley
- Jarod A. Zepp
- Gregory R. Grant
- Garret FitzGerald
- Amita Sehgal
- G. Scott Worthen
- David B. Frank
- Edward E. Morrisey
- Shaon Sengupta
Enabling scientific discoveries that improve human health