Excretory/secretory products from Hymenolepis nana adult worms alleviate ulcerative colitis in mice via tuft/IL-13 signaling pathway.

IF 3 2区 医学 Q1 PARASITOLOGY
Rong Mou, Xuanyin Cui, Hongyan Wang, Zhenfen Zhang, Yi Cheng, Wenlan Wu, Jinfu Li, Ke Zhang
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引用次数: 0

Abstract

Background: Hymenolepis nana (H. nana) is a zoonotic parasitic worm that parasitizes the small intestines of humans and rodents. Ulcerative colitis (UC) is a chronic and recurrent inflammatory bowel disease. Current symptom-based clinical treatments do not alter the natural course of UC, and mucosal healing has become a primary therapeutic goal for UC. However, the regulatory role of excretory/secretory products (ESPs) from H. nana adult worms in repairing the damaged intestinal mucosal barrier remains unclear.

Methods: This study investigated the protective effects of ESPs on intestinal mucosal integrity by using a dextran sulfate sodium (DSS)-induced colitis mouse model and a mouse small intestine organoid inflammation model. Histopathological alterations of mouse intestinal tissues were determined by pathological staining; the alterations in mucins, tight junction proteins, cytokines, and the number of various intestinal cells were detected by Western blotting (WB), immunohistochemistry (IHC), immunofluorescence (IF) and real-time quantitative polymerase chain reaction (RT-qPCR), etc. RESULTS: ESPs significantly improved DSS-induced intestinal damage in mice. Meanwhile, ESPs increased mucins and tight junction proteins expression and promoted intestinal stem cell proliferation and differentiation, thereby maintaining intestinal mucosal barrier integrity and alleviating UC in mice. In the DSS-induced inflamed small intestinal organoid model, ESPs reduced organoid damage and promoted the proliferation and differentiation of intestinal stem cells. The protective mechanism of ESPs might be related to the activation of the tuft/IL-13 signaling pathway, regulating intestinal barrier function and promoting the regeneration of intestinal stem cells.

Conclusions: In conclusion, H. nana-derived ESPs intervention facilitates healing of intestinal mucosa to alleviate UC in mice, enriching the feasibility and selectivity of "helminthic therapy."

微小膜膜绦虫成虫的排泄/分泌产物通过簇/IL-13信号通路缓解小鼠溃疡性结肠炎。
背景:微小膜膜绦虫(H. nana)是一种寄生于人类和啮齿动物小肠的人畜共患寄生虫。溃疡性结肠炎(UC)是一种慢性、复发性炎症性肠病。目前以症状为基础的临床治疗并不能改变UC的自然病程,粘膜愈合已成为UC的主要治疗目标。然而,纳纳H.成虫的排泄/分泌产物(ESPs)在修复受损肠粘膜屏障中的调节作用尚不清楚。方法:采用葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎模型和小鼠小肠类器官炎症模型,研究ESPs对小肠粘膜完整性的保护作用。病理染色观察小鼠肠组织病理变化;采用Western blotting (WB)、免疫组化(IHC)、免疫荧光(IF)、实时定量聚合酶链式反应(RT-qPCR)等方法检测各组肠黏膜蛋白、紧密连接蛋白、细胞因子及肠各细胞数量的变化。结果:ESPs可显著改善dss诱导的小鼠肠道损伤。同时,ESPs增加粘蛋白和紧密连接蛋白的表达,促进肠道干细胞的增殖和分化,从而维持肠道粘膜屏障的完整性,减轻小鼠UC。在dss诱导的炎性小肠类器官模型中,ESPs可减轻类器官损伤,促进肠道干细胞的增殖和分化。ESPs的保护机制可能与激活tuft/IL-13信号通路,调节肠道屏障功能,促进肠道干细胞再生有关。结论:综上所述,nanh来源的ESPs干预促进肠道黏膜愈合,减轻小鼠UC,丰富了“蠕虫治疗”的可行性和选择性。
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来源期刊
Parasites & Vectors
Parasites & Vectors 医学-寄生虫学
CiteScore
6.30
自引率
9.40%
发文量
433
审稿时长
1.4 months
期刊介绍: Parasites & Vectors is an open access, peer-reviewed online journal dealing with the biology of parasites, parasitic diseases, intermediate hosts, vectors and vector-borne pathogens. Manuscripts published in this journal will be available to all worldwide, with no barriers to access, immediately following acceptance. However, authors retain the copyright of their material and may use it, or distribute it, as they wish. Manuscripts on all aspects of the basic and applied biology of parasites, intermediate hosts, vectors and vector-borne pathogens will be considered. In addition to the traditional and well-established areas of science in these fields, we also aim to provide a vehicle for publication of the rapidly developing resources and technology in parasite, intermediate host and vector genomics and their impacts on biological research. We are able to publish large datasets and extensive results, frequently associated with genomic and post-genomic technologies, which are not readily accommodated in traditional journals. Manuscripts addressing broader issues, for example economics, social sciences and global climate change in relation to parasites, vectors and disease control, are also welcomed.
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