Knockdown of Cav2.2 Calcium Channel in Macrophages Aggravates Colitis Induced by Dextran Sodium Sulfate

IF 1.3 4区 生物学 Q4 CELL BIOLOGY
Genes to Cells Pub Date : 2025-09-21 DOI:10.1111/gtc.70051
Hironao Saegusa, Xiaoxu Li, Xinshuang Wang, Tsutomu Tanabe
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引用次数: 0

Abstract

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.

葡聚糖硫酸钠诱导巨噬细胞Cav2.2钙通道下调加重结肠炎
电压依赖性钙通道(VDCCs)以前被认为在可兴奋细胞中起作用,但最近越来越多的证据表明它们在不可兴奋细胞(如小胶质细胞)中也起作用。在本研究中,我们研究了n型VDCC (Cav2.2)在炎症性肠病(IBD)小鼠模型中巨噬细胞(一种不可兴奋的细胞)中的作用。将广泛应用于IBD化学诱导模型的葡聚糖硫酸钠(DSS)结肠炎模型应用于Cav2.2敲低(KD)小鼠,其中他莫昔芬可下调巨噬细胞中Cav2.2的表达。口服2.5% DSS 7天后,Cav2.2KD小鼠结肠炎疾病活动指数明显高于野生型(WT)小鼠,DSS处理小鼠结肠的组织学检查也表明,Cav2.2KD小鼠的肠道损伤更为严重。此外,Cav2.2KD小鼠结肠中Iba1+细胞(巨噬细胞/树突状细胞)的密度也升高。ELISA实验结果显示,Cav2.2KD小鼠体内TNFα水平明显升高。总的来说,这些数据表明Cav2.2KD小鼠比WT小鼠有更严重的结肠炎症。因此,巨噬细胞中的Cav2.2可能在抑制肠道免疫系统炎症中发挥一定作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Genes to Cells
Genes to Cells 生物-细胞生物学
CiteScore
3.40
自引率
0.00%
发文量
71
审稿时长
3 months
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.
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