恒河猴结肠炎模型的肠道蛋白组特征
  • DSS处理及SIV感染诱导产生2种实验性结肠炎的恒河猴模型,蛋白组学分析检测到恒河猴结肠组织中的2500多种蛋白;
  • DSS诱导的结肠炎恒河猴的蛋白表达模式类似于溃疡性结肠炎患者的蛋白组;
  • 与对照相比,DSS诱导的结肠炎恒河猴中线粒体能量代谢(包括脂肪酸代谢)相关蛋白的表达降低,而先天性免疫活化通路相关蛋白(包括补体及凝血蛋白)的表达增加;
  • SIV诱导的结肠炎恒河猴中与病毒防御相关的先天性免疫应答增加。
主编推荐语
沈志勋
Mucosal Immunology上发表的一项最新研究,通过DSS处理及SIV感染建立了2种不同的实验性结肠炎恒河猴模型,并通过蛋白组学分析鉴定出了恒河猴结肠炎模型的肠道蛋白表达特征变化,并发现DSS诱导的恒河猴结肠炎模型的肠道蛋白组类似于溃疡性结肠炎患者,可作为IBD研究的工具。
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Mucosal Immunology [IF:7.352]

Intestinal proteomic analysis of a novel non-human primate model of experimental colitis reveals signatures of mitochondrial and metabolic dysfunction

对非人灵长类实验性结肠炎模型的肠道蛋白组分析揭示线粒体特征及代谢功能失调

10.1038/s41385-019-0200-2

2019-09-03, Article

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Animal models recapitulating features of chronic colitis, such as ulcerative colitis, Crohn’s disease, or HIV infection, are critical to study disease pathogenesis and test novel therapeutics. In this study, we used a proteomics approach to explore the molecular intestinal response in two rhesus macaque (RM) animal models of experimentally induced colitis using dextran sulfate sodium (DSS) and simian immunodeficiency virus (SIV) infection. Proteomic analysis detected more than 2500 proteins in colonic tissue collected from 30 RMs. Differential protein expression analysis revealed a protein expression pattern in DSS-treated RMs resembling the proteome of human ulcerative colitis. In a group of 12 DSS-treated RMs compared to 6 with no treatment, decrease in expression of proteins related to mitochondrial energy metabolism, including fatty acid metabolism was noted, while innate immune activation pathways, including complement and coagulation proteins were upregulated. SIV infection of RMs resulted in increased innate immune responses related to viral defense. Proteomic signatures of barrier damage were apparent in both DSS treatment or SIV infection. These results demonstrate that DSS treatment in a non-human primate model resembles features of human ulcerative colitis, making this a promising tool to study important immunological mechanisms in inflammatory bowel disease.

First Authors:
Peter McQueen

Correspondence Authors:
Adam Burgener

All Authors:
Peter McQueen,Kathleen Busman-Sahay,Florian Rieder,Laura Noël-Romas,Stuart McCorrister,Garrett Westmacott,Jacob D Estes,Adam Burgener

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