产气荚膜梭菌肠毒素和产气荚膜梭菌肠毒素受体结合域对紧密连接的大小选择性渗透增强调节。

IF 4 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Tissue Barriers Pub Date : 2025-01-01 Epub Date: 2025-02-05 DOI:10.1080/21688370.2025.2459963
Keisuke Tachibana, Sayaka Sugimura, Shuko Sakimura, Lin Bai, Hiroshi Aoyama, Hiroyuki Takeda, Yuki Niwa, Masahiro Nagahama, Masuo Kondoh
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引用次数: 0

摘要

利用产气荚膜梭菌肠毒素的受体结合片段(C-CPE194、c - cpet和c - cpe19)和产气荚膜梭菌肠毒素的受体结合片段(angubinin -1)分别作为claudin调节剂和角蛋白调节剂,以claudin为基础的双细胞紧密连接(TJ)和角蛋白为基础的三细胞TJ密封被证明可以增强大分子的粘膜渗透。在这里,我们比较了这些调节剂对人肠道Caco-2细胞TJ的活性。与angubinin -1相比,所有claudin调节剂都能更有效地放松TJ完整性,其效价顺序为c - cpe19 > C-CPE194 > c - cpem1,增强渗透的结果相似。以100µg/mL浓度c - cmpt和C-CPE194处理48 h,分别增强了20 kDa和70 kDa葡聚糖的渗透。以30µg/mL浓度的c - cpe19处理48 h可增强葡聚糖的渗透,分子量可达150 kDa。此外,与单独处理相比,双细胞TJ调节剂(如c - cmpt、C-CPE194和c - cmp19)和三细胞TJ调节剂(如angubinin -1)的联合处理显示出TJ疏松和渗透增强活性;具体来说,C-CPEm19和angubinin -1共处理增加了大分子(70 kDa和150 kDa)的渗透。这些发现表明,TJ调节剂可以作为尺寸选择性渗透增强剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Size-selective permeation-enhancing modulation of the tight junction by receptor-binding domains of Clostridium perfringens enterotoxin and Clostridium perfringens iota-toxin.

Modulation of claudin-based bicellular tight junction (TJ) and angulin-based tricellular TJ seals has been shown to enhance mucosal permeation of macromolecules, by using the receptor-binding fragments of Clostridium perfringens enterotoxin (C-CPE194, C-CPEmt, and C-CPEm19) and Clostridium perfringens iota-toxin (angubindin-1) as claudin modulators and an angulin modulator, respectively. Here, we compared the activity of these modulators on the TJ in human intestinal Caco-2 cells. All the claudin modulators loosened TJ integrity more potently compared to angubindin-1 with the order of potency being C-CPEm19 > C-CPE194 > C-CPEmt, and results for permeation enhancement were similar. Treatment with C-CPEmt and C-CPE194 at 100 µg/mL for 48 h enhanced the permeation of dextran sized 20 kDa and 70 kDa, respectively. Treatment with C-CPEm19 at 30 µg/mL for 48 h enhanced permeation of dextran with a molecular mass of up to 150 kDa. Furthermore, co-treatment of bicellular TJ modulators, such as C-CPEmt, C-CPE194, and C-CPEm19, and tricellular TJ modulators, such as angubindin-1, showed additive TJ-loosening and permeation-enhancing activities compared with individual treatments; specifically, C-CPEm19 and angubindin-1 co-treatment increased permeation of large molecules (70 kDa and 150 kDa). These findings indicate that TJ modulators may be used as size-selective permeation enhancers.

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来源期刊
Tissue Barriers
Tissue Barriers MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.60
自引率
6.50%
发文量
25
期刊介绍: Tissue Barriers is the first international interdisciplinary journal that focuses on the architecture, biological roles and regulation of tissue barriers and intercellular junctions. We publish high quality peer-reviewed articles that cover a wide range of topics including structure and functions of the diverse and complex tissue barriers that occur across tissue and cell types, including the molecular composition and dynamics of polarized cell junctions and cell-cell interactions during normal homeostasis, injury and disease state. Tissue barrier formation in regenerative medicine and restoration of tissue and organ function is also of interest. Tissue Barriers publishes several categories of articles including: Original Research Papers, Short Communications, Technical Papers, Reviews, Perspectives and Commentaries, Hypothesis and Meeting Reports. Reviews and Perspectives/Commentaries will typically be invited. We also anticipate to publish special issues that are devoted to rapidly developing or controversial areas of research. Suggestions for topics are welcome. Tissue Barriers objectives: Promote interdisciplinary awareness and collaboration between researchers working with epithelial, epidermal and endothelial barriers and to build a broad and cohesive worldwide community of scientists interesting in this exciting field. Comprehend the enormous complexity of tissue barriers and map cross-talks and interactions between their different cellular and non-cellular components. Highlight the roles of tissue barrier dysfunctions in human diseases. Promote understanding and strategies for restoration of tissue barrier formation and function in regenerative medicine. Accelerate a search for pharmacological enhancers of tissue barriers as potential therapeutic agents. Understand and optimize drug delivery across epithelial and endothelial barriers.
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