The Circadian Clock Gene BMAL1 Coordinates Intestinal Regeneration
| Autor: | Hanna Chang, Kyle Stokes, David R. Weaver, David T. Breault, Phillip Karpowicz, Abrial Cooke |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Hepatology Circadian clock Gastroenterology Life Sciences Inflammation Biology Intestinal epithelium 3. Good health Proinflammatory cytokine CLOCK 03 medical and health sciences 030104 developmental biology Endocrinology Precursor cell Internal medicine medicine Circadian rhythm medicine.symptom Loss function |
| Zdroj: | Biological Sciences Publications |
| ISSN: | 2352-345X |
| DOI: | 10.1016/j.jcmgh.2017.03.011 |
| Popis: | Background & Aims The gastrointestinal syndrome is an illness of the intestine caused by high levels of radiation. It is characterized by extensive loss of epithelial tissue integrity, which initiates a regenerative response by intestinal stem and precursor cells. The intestine has 24-hour rhythms in many physiological functions that are believed to be outputs of the circadian clock: a molecular system that produces 24-hour rhythms in transcription/translation. Certain gastrointestinal illnesses are worsened when the circadian rhythms are disrupted, but the role of the circadian clock in gastrointestinal regeneration has not been studied. Methods We tested the timing of regeneration in the mouse intestine during the gastrointestinal syndrome. The role of the circadian clock was tested genetically using the BMAL1 loss of function mouse mutant in vivo, and in vitro using intestinal organoid culture. Results The proliferation of the intestinal epithelium follows a 24-hour rhythm during the gastrointestinal syndrome. The circadian clock runs in the intestinal epithelium during this pathologic state, and the loss of the core clock gene, BMAL1, disrupts both the circadian clock and rhythmic proliferation. Circadian activity in the intestine involves a rhythmic production of inflammatory cytokines and subsequent rhythmic activation of the JNK stress response pathway. Conclusions Our results show that a circadian rhythm in inflammation and regeneration occurs during the gastrointestinal syndrome. The study and treatment of radiation-induced illnesses, and other gastrointestinal illnesses, should consider 24-hour timing in physiology and pathology. |
| Databáze: | OpenAIRE |
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