Genome-wide effect of pulmonary airway epithelial cell-specific Bmal1 deletion.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Zhenguang ZhangAndrew Loudon

Abstract

Pulmonary airway epithelial cells (AECs) form a critical interface between host and environment. We investigated the role of the circadian clock using mice bearing targeted deletion of the circadian gene brain and muscle ARNT-like 1 (Bmal1) in AECs. Pulmonary neutrophil infiltration, biomechanical function, and responses to influenza infection were all disrupted. A circadian time-series RNA sequencing study of laser-captured AECs revealed widespread disruption in genes of the core circadian clock and output pathways regulating cell metabolism (lipids and xenobiotics), extracellular matrix, and chemokine signaling, but strikingly also the gain of a novel rhythmic transcriptome in Bmal1-targeted cells. Many of the rhythmic components were replicated in primary AECs cultured in air-liquid interface, indicating significant cell autonomy for control of pulmonary circadian physiology. Finally, we found that metabolic cues dictate phasing of the pulmonary clock and circadian responses to immunologic challenges. Thus, the local circadian clock in AECs is vital in lung health by coordinating major cell processes such as metabolism and immunity.-Zhang, Z. Hunter, L., Wu, G., Maidstone, R., Mizoro, Y., Vonslow, R., Fife, M., Hopwood, T., ...Continue Reading

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Citations

Sep 29, 2019·Annual Review of Physiology·Charles NosalJeffrey A Haspel
Jul 9, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Colleen M Bartman, Y S Prakash
Dec 11, 2019·Immunology·Matthew Baxter, David W Ray
Jan 17, 2020·JCI Insight·Jeffrey A HaspelLaura A Solt
Nov 24, 2019·International Journal of Molecular Sciences·Sailen Barik
Apr 21, 2020·Frontiers in Endocrinology·Shuang ZhouHou-Zao Chen
Jan 3, 2020·The Journal of Clinical Investigation·Colleen M BartmanY S Prakash
Apr 22, 2020·Reviews in Medical Virology·George Anderson, Russel J Reiter
Jan 7, 2021·American Journal of Physiology. Lung Cellular and Molecular Physiology·Colleen M BartmanY S Prakash
Jan 3, 2021·Medical Hypotheses·Merve MercanNurettin Abacıoğlu
Jan 23, 2021·Journal of Biological Rhythms·Shaon SenguptaJane A McKeating
Dec 19, 2020·Current Opinion in Pharmacology·Nino ChiricoPieterjan Dierickx
Sep 23, 2021·Journal of Biological Rhythms·Yool LeeAmita Sehgal

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