Circadian disruption alters mouse lung clock gene expression and lung mechanics.
Most aspects of human physiology and behavior exhibit 24-h rhythms driven by a master circadian clock in the brain, which synchronizes peripheral clocks. Lung function and ventilation are subject to circadian regulation and exhibit circadian oscillations. Sleep disruption, which causes circadian disruption, is common in those with chronic lung disease, and in the general population; however, little is known about the effect on the lung of circadian disruption. We tested the hypothesis circadian disruption alters expression of clock genes in the lung and that this is associated with altered lung mechanics. Female and male mice were maintained on a 12:12-h light/dark cycle (control) or exposed for 4 wk to a shifting light regimen mimicking chronic jet lag (CJL). Airway resistance (Rn), tissue damping (G), and tissue elastance (H) did not differ between control and CJL females. Rn at positive end-expiratory pressure (PEEP) of 2 and 3 cmH(2)O was lower in CJL males compared with controls. G, H, and G/H did not differ between CJL and control males. Among CJL females, expression of clock genes, Bmal1 and Rev-erb alpha, was decreased; expression of their repressors, Per2 and Cry 2, was increased. Among CJL males, expression of Clock was decreased; Per 2 and Rev-erb alpha expression was increased. We conclude circadian disruption alters lung mechanics and clock gene expression and does so in a sexually dimorphic manner.
Lung Regeneration Laboratory, Department of Medicine, Georgetown University School of Medicine, Washington, District of Columbia, USA.
Hélène
H
Hadden
Steven J
SJ
Soldin
Donald
D
Massaro
D056930:ARNTL Transcription Factors / Q000235:genetics; D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics*; D021081:Chronobiology Disorders / Q000503:physiopathology*; D056931:Cryptochromes / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D020179:Jet Lag Syndrome / Q000378:metabolism / Q000503:physiopathology; D008168:Lung / Q000503:physiopathology*; D008297:Male; D051379:Mice; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000235:genetics; D056950:Period Circadian Proteins / Q000235:genetics; D012129:Respiratory Function Tests; D012737:Sex Factors
D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; C538967:Cry2 protein, mouse; D056931:Cryptochromes; C498262:Nr1d1 protein, mouse; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D056926:CLOCK Proteins