Urothelial collective-gliding response acts as a toll-like receptor 4-associated defense mechanism

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-09-12 DOI:10.1016/j.isci.2025.113553

Ning Zhang , Takeshi Sano , Katsuhiro Ito , Shinji Ito , Ryosuke Ikeuchi , Hideaki Takada , Kenji Nakamura , Toru Sakatani , Akihiro Hamada , Masashi Takeda , Kaoru Murakami , Yuki Kita , Takayuki Sumiyoshi , Takayuki Goto , Ryoichi Saito , Osamu Ogawa , Michiyuki Matsuda , Takashi Kobayashi

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引用次数: 0

Abstract

Collective cell migration (CCM) is characterized by the coordinated movement of cell groups while maintaining cell-to-cell cohesion. Despite extensive research on CCM, the collective migration of mature epithelial cells over the extracellular matrix in response to external stimuli has not been reported. Using intravital imaging in mice, we identified urothelial CCM (UCCM) triggered by immunogenic substances, including bladder cancer cells (MB49) and uropathogenic Escherichia coli (UPEC). Integrin signaling inhibitors suppress UCCM, significantly enhancing MB49 tumor growth and UPEC bladder infection. UCCM initiation involves Toll-like receptor 4 (TLR4), we designated this TLR4-associated UCCM as the urothelial collective-gliding response (UCGR). Downstream of integrin signaling, urothelial matrix metalloproteinases (MMP)-8 and MMP-9 mediate UCGR. Intravesical instillation of these factors accelerates UCCM and inhibits tumor growth and infection. UCGR may represent a TLR4-associated defense mechanism, offering potential therapeutic strategies for bladder disorders such as refractory cystitis and recurrent non-muscle invasive bladder cancer after endoscopic resection.

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尿路上皮集体滑动反应是toll样受体4相关的防御机制

细胞集体迁移（CCM）的特点是细胞群的协调运动，同时保持细胞间的内聚。尽管对CCM进行了广泛的研究，但成熟上皮细胞在响应外部刺激时在细胞外基质上的集体迁移尚未报道。通过小鼠活体成像，我们鉴定了由免疫原性物质触发的尿路上皮CCM (UCCM)，包括膀胱癌细胞（MB49）和尿路致病性大肠杆菌（UPEC）。整合素信号抑制剂抑制UCCM，显著促进MB49肿瘤生长和UPEC膀胱感染。UCCM的启动涉及toll样受体4 (TLR4)，我们将这种TLR4相关的UCCM称为尿路上皮集体滑动反应（UCGR）。在整合素信号的下游，尿路上皮基质金属蛋白酶(MMP)-8和MMP-9介导UCGR。膀胱内灌注这些因子加速UCCM，抑制肿瘤生长和感染。UCGR可能代表了tlr4相关的防御机制，为难治性膀胱炎和内镜切除后复发性非肌性浸润性膀胱癌等膀胱疾病提供了潜在的治疗策略。

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

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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