Long-term exposure to constant light disrupts intestinal stem cells through sympathoexcitation-induced Wnt5a signaling inhibition.

BACKGROUND: Long-term exposure to constant light is becoming a prevalent lifestyle that is associated with irritable bowel syndrome (IBS), a chronic functional gastrointestinal disorder. Intestinal stem cells (ISCs) are an important population of cells that maintain homeostasis and function of intestinal tissues. The purpose of this study was to identify the effects of long-term constant light exposure on gastrointestinal function and the potential mechanisms of sympathetic activity on ISC. METHODS: Rats housed in a 24 h constant light chamber for 4 weeks were used as the constant light exposure animal model. Hematoxylin-eosin staining and immunohistochemical examination were used to determine the pathological changes of the intestine. Propranolol (ARs inhibitor; 40 mg/kg/day), metoprolol (ADRβ1 inhibitor; 50 mg/kg/day), and Box5 (Wnt5a inhibitor; 2 μg/day) were used to examine the effect of sympathoexcitation and Wnt signaling pathway on constant light-induced gastrointestinal disorders. RESULTS: We found that 4 weeks of constant light exposure in rats resulted in a decrease in the number of ISC and an increase in sympathetic activity. Intestinal β1-adrenoceptor expression and reactive oxygen species (ROS) were significantly increased, but Wnt5a expression decreased in the continuous light-exposed rats. Similarly, we found that administration of the β1-adrenoceptor antagonist metoprolol for 4 weeks attenuated the effects of continuous light exposure on the intestine, which was rescued by the reintroduction of Wnt5a. CONCLUSION: Taken together, these data indicate that sympathoexcitation is critical for disruption of ISC under constant light exposure, suggesting that targeting β1-adrenoceptor/oxidative stress/Wnt5a axis may be a potential strategy for ISC disruption induced by prolonged sustained light exposure, providing a new direction for IBS treatment.