Table 1.
Role of the Molecular Clock in Lung Pathophysiology
| Agents and Models Used in Pulmonary Circadian Clock Studies | Major Outcomes/Findings | References |
|---|---|---|
| Lung circadian timing in C57BL/6J and PER2::Luc transgenic mice | Clara/Club cells are critical for maintaining clock function in lung tissue | 5 |
| Diurnal oscillations in the lung transcriptome in Wistar rats | Genes involved in the metabolism and transport of endogenous compounds and xenobiotics in clock control of lung pathophysiology | 7 |
| A repeated light-shifting regimen (simulated jet lag model) in C57BL/6J mice | Disturbing molecular clock function alters lung mechanics in a sexually dimorphic manner | 6 |
| Cigarette smoke exposure in Sprague-Dawley rats | Transcriptomic changes in lung clock gene expression | 8 |
| Cigarette smoke exposure in C57BL/6J and A/J mice | Suppression of clock gene, Nr1d1, which encodes Rev-erbα | 11 |
| Cigarette smoke exposure in C57BL/6J mice (COPD/emphysema model) | Circadian clock dysfunction is associated with increased lung inflammation via the SIRT1–BMAL1 pathway | 10 |
| Circadian clock regulates Nrf2-mediated antioxidant defense pathway by bleomycin in mice | Circadian clock as an endogenous regulatory mechanism controlling the rhythmic activity of the redox-sensitive Nrf2 in the lung | 9 |
| Circadian rhythm reprogramming by LPS in mice | Genome-wide expression of clock genes during LPS-induced lung inflammation | 13 |
| Host defense to bacterial infection and pulmonary inflammation by LPS in mice | Genetic ablation of Bmal1 in bronchiolar cells disrupts rhythmic Cxcl5 expression | 14 |
| Influenza A virus–dependent remodeling of pulmonary clock function in mouse model of COPD/emphysema | Chronic cigarette smoke exposure combined with influenza A virus infection altered the timing of clock gene expression, along with increased lung inflammation, and disrupted rhythms of lung function | 12 |
Definition of abbreviations: BMAL1, brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1; Clock, circadian locomotor output cycles protein kaput; COPD, chronic obstructive pulmonary disease; Cxcl5, chemokine (C-X-C) motif ligand 5; Luc, luciferase; Nrf2, nuclear factor (erythroid-derived 2)-like 2; Nr1d1, nuclear receptor subfamily 1, Group D, member 1; PER2, period 2; SIRT1, sirtuin 1.