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Related Concept Videos

Circadian Rhythms and Gene Regulation02:19

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The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
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Related Experiment Video

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In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells
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Circadian molecular clock in lung pathophysiology.

Isaac K Sundar1, Hongwei Yao1, Michael T Sellix2

  • 1Department of Environmental Medicine, Lung Biology and Disease Program, University of Rochester Medical Center, Rochester, New York; and.

American Journal of Physiology. Lung Cellular and Molecular Physiology
|September 13, 2015
PubMed
Summary

Disrupted circadian rhythms in the lungs are linked to chronic airway diseases. Restoring molecular clock function offers a new target for treating lung inflammation and disease.

Keywords:
BMAL1COPDPER2REV-ERBαRORαasthmabiomarkersfibrosis

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Area of Science:

  • Pulmonary Medicine
  • Chronobiology
  • Immunology

Background:

  • Chronic airway diseases exhibit disrupted circadian rhythms in lung function and inflammation.
  • Molecular clock gene transcription factors (e.g., BMAL1:CLOCK, PERIOD, CRYPTOCHROME) regulate these rhythms.
  • Key regulators like REV-ERBα, RORα, and SIRT1 influence clock stability and function.

Purpose of the Study:

  • To provide a comprehensive overview of clock-controlled functions in the lungs.
  • To highlight the impact of circadian clock disruption on chronic airway disease pathophysiology and exacerbations.
  • To explore the potential of the molecular clock as a chronopharmacological target.

Main Methods:

  • Review of existing literature on molecular clock mechanisms in lung physiology and disease.
  • Analysis of how environmental factors (exposomes, smoke, infections) alter clock function.
  • Examination of the interplay between the molecular clock, immune responses, and lung pathophysiology.

Main Results:

  • Circadian clock dysfunction is implicated in immune and inflammatory responses to various environmental agents and pathogens.
  • Environmental stressors and redox modulation can disrupt clock regulators (REV-ERBα, RORα) and promote DNA damage, senescence, and inflammation.
  • A reciprocal relationship exists between the lung's molecular clock and its immune/inflammatory status.

Conclusions:

  • Molecular clock function in lung cells can serve as a biomarker for disease severity and exacerbations.
  • The molecular clock represents a novel chronopharmacological target for managing lung pathophysiology.
  • Understanding circadian clock mechanisms is crucial for developing effective chronotherapies for chronic airway diseases.