Circadian molecular clock disruption in chronic pulmonary diseases.

The circadian clock is the biochemical oscillator with a near 24-h period that is responsible for generating the circadian rhythms in peripheral organs including the lung. Mounting evidence suggests that circadian clock disruption during chronic lung diseases plays an essential role in augmented oxidative stress, inflammatory response, metabolic imbalances, hypoxia/hyperoxia, mucus secretion, dysregulated autophagy, and alters pulmonary function. Here, we review circadian clock disruption and discuss candidate clock genes that are altered at the transcriptional or translational level in chronic pulmonary diseases. This review aims to provide the current knowledge and understanding of the circadian molecular clock disruption in chronic pulmonary diseases which will further advance the development of novel clock-based therapeutics in the future. Circadian clock disruption in the lung is associated with chronic pulmonary diseases such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (PF), cystic fibrosis (CF), pulmonary arterial hypertension (PAH), and lung cancer. Cumulative evidence from preclinical models demonstrates the promising role of the circadian clock in modulating immune response and other associated phenotypes observed in chronic pulmonary diseases. Understanding the core molecular mechanisms contributing to circadian clock disruption in chronic lung diseases will help advance the development of novel clock-based therapeutics in the future. [ABSTRACT FROM AUTHOR]