{"title":"葡聚糖硫酸钠诱导巨噬细胞Cav2.2钙通道下调加重结肠炎","authors":"Hironao Saegusa, Xiaoxu Li, Xinshuang Wang, Tsutomu Tanabe","doi":"10.1111/gtc.70051","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Voltage-dependent calcium channels (VDCCs) have previously been thought to be functional in excitable cells, but recently accumulating evidence suggests that they are also functional in non-excitable cells such as microglia. In the present study, we investigated the role of the N-type VDCC (Cav2.2) in macrophages, a kind of non-excitable cell, in a mouse model of inflammatory bowel disease (IBD). The dextran sodium sulfate (DSS) colitis model, a widely used chemically induced model of IBD, was applied to Cav2.2 knockdown (KD) mice, where Cav2.2 expression in macrophages can be downregulated by the application of tamoxifen. After the 7 days of oral administration of 2.5% DSS, Cav2.2KD mice had a significantly higher disease activity index for colitis compared to wild-type (WT) mice, and histological examination of the colon from DSS-treated mice also suggested more severe intestinal damage in Cav2.2KD mice. Moreover, the densities of Iba1<sup>+</sup> cells (macrophages/dendritic cells) in the colon were also elevated in Cav2.2KD mice. TNFα levels were significantly higher in Cav2.2KD mice as revealed by ELISA experiments. Collectively, these data suggest that the Cav2.2KD mice had more severe colonic inflammation compared to WT mice. Therefore, Cav2.2 in macrophages may play some roles in suppressing inflammation in the intestinal immune system.</p>\n </div>","PeriodicalId":12742,"journal":{"name":"Genes to Cells","volume":"30 5","pages":""},"PeriodicalIF":1.3000,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Knockdown of Cav2.2 Calcium Channel in Macrophages Aggravates Colitis Induced by Dextran Sodium Sulfate\",\"authors\":\"Hironao Saegusa, Xiaoxu Li, Xinshuang Wang, Tsutomu Tanabe\",\"doi\":\"10.1111/gtc.70051\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>Voltage-dependent calcium channels (VDCCs) have previously been thought to be functional in excitable cells, but recently accumulating evidence suggests that they are also functional in non-excitable cells such as microglia. In the present study, we investigated the role of the N-type VDCC (Cav2.2) in macrophages, a kind of non-excitable cell, in a mouse model of inflammatory bowel disease (IBD). The dextran sodium sulfate (DSS) colitis model, a widely used chemically induced model of IBD, was applied to Cav2.2 knockdown (KD) mice, where Cav2.2 expression in macrophages can be downregulated by the application of tamoxifen. After the 7 days of oral administration of 2.5% DSS, Cav2.2KD mice had a significantly higher disease activity index for colitis compared to wild-type (WT) mice, and histological examination of the colon from DSS-treated mice also suggested more severe intestinal damage in Cav2.2KD mice. Moreover, the densities of Iba1<sup>+</sup> cells (macrophages/dendritic cells) in the colon were also elevated in Cav2.2KD mice. TNFα levels were significantly higher in Cav2.2KD mice as revealed by ELISA experiments. Collectively, these data suggest that the Cav2.2KD mice had more severe colonic inflammation compared to WT mice. Therefore, Cav2.2 in macrophages may play some roles in suppressing inflammation in the intestinal immune system.</p>\\n </div>\",\"PeriodicalId\":12742,\"journal\":{\"name\":\"Genes to Cells\",\"volume\":\"30 5\",\"pages\":\"\"},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2025-09-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genes to Cells\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/gtc.70051\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genes to Cells","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/gtc.70051","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Knockdown of Cav2.2 Calcium Channel in Macrophages Aggravates Colitis Induced by Dextran Sodium Sulfate
Voltage-dependent calcium channels (VDCCs) have previously been thought to be functional in excitable cells, but recently accumulating evidence suggests that they are also functional in non-excitable cells such as microglia. In the present study, we investigated the role of the N-type VDCC (Cav2.2) in macrophages, a kind of non-excitable cell, in a mouse model of inflammatory bowel disease (IBD). The dextran sodium sulfate (DSS) colitis model, a widely used chemically induced model of IBD, was applied to Cav2.2 knockdown (KD) mice, where Cav2.2 expression in macrophages can be downregulated by the application of tamoxifen. After the 7 days of oral administration of 2.5% DSS, Cav2.2KD mice had a significantly higher disease activity index for colitis compared to wild-type (WT) mice, and histological examination of the colon from DSS-treated mice also suggested more severe intestinal damage in Cav2.2KD mice. Moreover, the densities of Iba1+ cells (macrophages/dendritic cells) in the colon were also elevated in Cav2.2KD mice. TNFα levels were significantly higher in Cav2.2KD mice as revealed by ELISA experiments. Collectively, these data suggest that the Cav2.2KD mice had more severe colonic inflammation compared to WT mice. Therefore, Cav2.2 in macrophages may play some roles in suppressing inflammation in the intestinal immune system.
期刊介绍:
Genes to Cells provides an international forum for the publication of papers describing important aspects of molecular and cellular biology. The journal aims to present papers that provide conceptual advance in the relevant field. Particular emphasis will be placed on work aimed at understanding the basic mechanisms underlying biological events.