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在结肠炎小鼠模型中,感染Ancylostoma caninum 排泄/分泌产物后蛋白表达的变化。

Changes in protein expression after treatment with Ancylostoma caninum excretory/secretory products in a mouse model of colitis.

机构信息

Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.

QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.

出版信息

Sci Rep. 2017 Feb 13;7:41883. doi: 10.1038/srep41883.

Abstract

Different reports have highlighted the potential use of helminths and their secretions in the treatment of inflammatory bowel disease (IBD) conditions; however, no reports have investigated their effects at a proteome level. Herein, we characterise the protein expression changes that occur in lamina propria (LP) and the intestinal epithelial cells (IEC) of mice with dextran sulfate sodium (DSS)-induced colitis treated with Ancylostoma caninum excretory/secretory (ES) products using a quantitative proteomic approach. We have shown how parasite products can significantly alter the expression of proteins involved in immune responses, cell death and with an antioxidant activity. Interestingly, significant changes in the expression levels of different mucins were observed in this study. MUC13, a mucin implicated in gastrointestinal homeostasis, was upregulated in the LP of mice with DSS-induced colitis treated with ES, while MUC2, a major component of mucus, was upregulated in the IEC. In addition, A. caninum proteins have an important effect on proteins with antioxidant functions and proteins involved in intestinal homeostasis and tissue integrity and regeneration. Understanding how parasites can ameliorate IBD pathogenesis can help us design novel treatments for autoimmune diseases.

摘要

不同的报告强调了寄生虫及其分泌物在治疗炎症性肠病(IBD)方面的潜在用途;然而,尚无报告研究它们在蛋白质组水平上的作用。在此,我们采用定量蛋白质组学方法,研究了旋毛虫排泄物/分泌物(ES)产物对葡聚糖硫酸钠(DSS)诱导结肠炎小鼠的固有层(LP)和肠上皮细胞(IEC)中发生的蛋白质表达变化进行了描述。我们已经表明寄生虫产物如何能显著改变参与免疫反应、细胞死亡和具有抗氧化活性的蛋白质的表达。有趣的是,在这项研究中观察到不同粘蛋白表达水平的显著变化。MUC13 是一种与胃肠道内稳态有关的粘蛋白,在 DSS 诱导的结肠炎小鼠的 LP 中上调,而 MUC2 是粘液的主要成分,在 IEC 中上调。此外,旋毛虫蛋白对具有抗氧化功能的蛋白质以及参与肠道内稳态和组织完整性和再生的蛋白质有重要影响。了解寄生虫如何改善 IBD 的发病机制可以帮助我们为自身免疫性疾病设计新的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef20/5304188/cede794e63f3/srep41883-f1.jpg

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