肠易激综合征
敏化
TRPV1型
中枢敏化
医学
行为敏化
胃肠病学
免疫学
内科学
伤害
瞬时受体电位通道
受体
伏隔核
作者
Hao‐Nan Zheng,Yu‐Ru Zhi,Yang‐Shuai Su,Jin‐Yan Jiang,Hao‐Zhou Zhang,Feng Cao,Y Wang,Yan Chi,Ying Zhang
摘要
Abstract Background Visceral hypersensitivity is considered the core pathophysiological mechanism that causes abdominal pain in patients with irritable bowel syndrome (IBS). Fungal dysbiosis has been proved to contribute to visceral hypersensitivity in IBS patients. However, the underlying mechanisms for Dectin‐1, a major fungal recognition receptor, in visceral hypersensitivity are poorly understood. This study aimed to explore the role of Dectin‐1 in visceral hypersensitivity and elucidate the impact of Dectin‐1 activity on the function of transient receptor potential vanilloid type 1 (TRPV1). Methods Visceral hypersensitivity model was established by the intracolonic administration of 0.1 mL TNBS (130 μg/mL in 30% ethanol) in the male mice. Fluconazole and nystatin were used as fungicides. Laminarin, a Dectin‐1 antagonist and gene knockout ( Clec7a −/− ) mice were used to interrupt the function of Dectin‐1. Colorectal distension‐electromyogram recording was performed to assess visceral sensitivity. Immunostaining experiment was performed to determine the localization of Dectin‐1 in dorsal root ganglion (DRG) neurons. Calcium imaging study was performed to assay TRPV1‐mediated calcium influx in acutely dissociated DRG neurons. Results Pretreatment with fungicides, administration of laminarin or genetic deletion of Clec7a alleviated TNBS‐induced visceral hypersensitivity in male mice. The expression of Dectin‐1 was upregulated in the DRG and colon of TNBS‐treated mice. Colocalization of Dectin‐1 and TRPV1 was observed in DRG neurons. Importantly, pretreatment with curdlan, a Dectin‐1 agonist, increased TRPV1‐mediated calcium influx. Conclusions Dectin‐1 contributes to visceral hypersensitivity in IBS or in inflammatory bowel disease in remission and activation of Dectin‐1 induces TRPV1 sensitization. Significance Statement This work provides direct evidence for the functional regulation of TRPV1 channel by Dectin‐1 activity, proposing a new mechanism underlying TRPV1 sensitization. Control of intestinal fungi might be beneficial for the treatment of refractory abdominal pain in patients with IBS or IBD in remission.
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