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肠道类器官反映的犬炎症性肠病痕迹。

Traces of Canine Inflammatory Bowel Disease Reflected by Intestinal Organoids.

机构信息

Clinic for Small Animals, Division for Small Animal Internal Medicine, Department for Small Animal and Horses, University of Veterinary Medicine, 1210 Vienna, Austria.

Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.

出版信息

Int J Mol Sci. 2024 Jan 1;25(1):576. doi: 10.3390/ijms25010576.

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory condition that affects humans and several domestic animal species, including cats and dogs. In this study, we have analyzed duodenal organoids derived from canine IBD patients using quantitative proteomics. Our objective was to investigate whether these organoids show phenotypic traits of the disease compared with control organoids obtained from healthy donors. To this aim, IBD and control organoids were subjected to quantitative proteomics analysis via liquid chromatography-mass spectrometry. The obtained data revealed notable differences between the two groups. The IBD organoids exhibited several alterations at the levels of multiple proteins that are consistent with some known IBD alterations. The observed phenotype in the IBD organoids to some degree mirrors the corresponding intestinal condition, rendering them a compelling approach for investigating the disease and advancing drug exploration. Additionally, our study revealed similarities to some human IBD biomarkers, further emphasizing the translational and comparative value of dogs for future investigations related to the causes and treatment of IBD. Relevant proteins such as CALU, FLNA, MSN and HMGA2, which are related to intestinal diseases, were all upregulated in the IBD duodenal organoids. At the same time, other proteins such as intestinal keratins and the mucosal immunity PIGR were depleted in these IBD organoids. Based on these findings, we propose that these organoids could serve as a valuable tool for evaluating the efficacy of therapeutic interventions against canine IBD.

摘要

炎症性肠病(IBD)是一种慢性炎症性疾病,影响人类和包括猫和狗在内的几种家养动物。在这项研究中,我们使用定量蛋白质组学分析了来自犬 IBD 患者的十二指肠类器官。我们的目的是研究这些类器官是否与来自健康供体的对照类器官相比表现出疾病的表型特征。为此,我们通过液相色谱-质谱对 IBD 和对照类器官进行了定量蛋白质组学分析。获得的数据显示两组之间存在明显差异。IBD 类器官在多个蛋白质水平上表现出几种改变,这些改变与一些已知的 IBD 改变一致。IBD 类器官观察到的表型在某种程度上反映了相应的肠道状况,使它们成为研究疾病和推进药物探索的有力方法。此外,我们的研究还揭示了与一些人类 IBD 生物标志物的相似性,进一步强调了狗在未来与 IBD 的病因和治疗相关的研究中的转化和比较价值。CALU、FLNA、MSN 和 HMGA2 等与肠道疾病相关的相关蛋白在 IBD 十二指肠类器官中均上调。同时,这些 IBD 类器官中其他蛋白如肠道角蛋白和黏膜免疫 PIGR 被耗尽。基于这些发现,我们提出这些类器官可以作为评估针对犬 IBD 的治疗干预效果的有价值的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d98a/10778911/8db901692605/ijms-25-00576-g001.jpg

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