Activation of 5-Hydroxytryptamine 4 Receptor Improves Colonic Barrier Function by Triggering Mucin 2 Production in a Mouse Model of Type 1 Diabetes

作者全名："Han, Changhao; Geng, Qinghua; Qin, Jingjing; Li, Yulin; Yu, Huarong"

作者地址："[Han, Changhao; Geng, Qinghua; Qin, Jingjing; Li, Yulin; Yu, Huarong] Chongqing Med Univ, Dept Physiol, Chongqing, Peoples R China; [Yu, Huarong] Chongqing Med Univ, Dept Physiol, 1 Yixueyuan Rd,Yuz-hong Dist, Chongqing 400016, Peoples R China"

通信作者："Yu, HR (通讯作者)，Chongqing Med Univ, Dept Physiol, 1 Yixueyuan Rd,Yuz-hong Dist, Chongqing 400016, Peoples R China."

来源：AMERICAN JOURNAL OF PATHOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000813216300005

JCR分区：Q1

影响因子：6

年份：2022

卷号：192

期号：6

开始页：876

结束页：886

文献类型：Article

关键词：　

摘要："Diabetes leads to intestinal barrier dysfunction. 5-Hydroxytryptamine 4 receptor (5-HT4R) is distributed in the colonic mucosa, but little is known about the role of its activation in diabetes-evoked colonic barrier dysfunction. This study investigates whether activation of 5-HT(4)Rs on goblet cells (GCs) protects the colon from commensal bacterial translocation in diabetic mice. Expression of 5-HT4R detected inside the colonic epithelium by RNAscope in situ hybridization was further observed within the mucin 2 (MUC2)-immunoreactive GCs. In diabetic mice, neither 5-HT4R transcription nor protein levels were altered compared with those in nondiabetic mice. Bacterial translocation was characterized by 16S rRNA RNAscope in situ hybridization and manifested in both crypts and lamina propria of the colon in diabetic mice. Mucin production and MUC2 expression were significantly decreased in diabetic mice. Furthermore, the loss of mitochondrial cristae of GCs and the down-regulation of mitofilin, the core protein maintaining mitochondrial homeostasis, were observed in diabetic mice. Long-term treatment with 5-HT4R agonist in diabetic mice not only prevented bacterial penetration of the whole colonic mucosa but also promoted mucin production and MUC2 expression. Markedly, 5-HT4R agonist also restored the mitochondrial cristae of GCs and up-regulated mitofilin. However, co-administration of 5-HT4R antagonist abolished the effects of 5-HT4R agonist on diabetic mice. These findings indicate that 5-HT4R in colonic mucosa is an effective target for the treatment of diabetes-induced colonic mucous barrier dysfunction."

基金机构：hongqing Science and Technology Commission [CSTC2014JCYJA10014]

基金资助正文：Supported by Cuttingedge Research Project of the Chongqing Science and Technology Commission grant CSTC2014JCYJA10014 (H.Y.)