Significance of Luminal Exosomes in Inflammatory Bowel Disease (IBD)

管腔外泌体在炎症性肠病 (IBD) 中的意义

• 批准号: 8870956
• 负责人: Alan Colm Moss
• 金额: $ 8.7万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8870956
• 关键词: Abnormal Cell; Affect; American; Antineoplastic Agents; Biological Markers; Biopsy; Blood; Caliber; Cell physiology; Cells; Cellular biology; Characteristics; Chronic; Colitis; Colonoscopy; Communication; Data; Detection; Diagnostic; Disease; Disease Marker; Ecology; Enzyme-Linked Immunosorbent Assay; Enzymes; Epithelial Cells; Exhibits; Feces; Funding; Future; Gene Expression; Gene Expression Profile; Gene Expression Profiling; Goals; Grant; Heating; Immune; Incubated; Individual; Inflammation Mediators; Inflammatory; Inflammatory Bowel Diseases; Inflammatory disease of the intestine; Intestinal Content; Intestinal Mucosa; Intestines; Label; Lamina Propria; Lateral; Leukocytes; Life Cycle Stages; Liquid substance; Location; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Mediator of activation protein; Membrane; Mentors; Messenger RNA; Metabolic; MicroRNAs; Migration Assay; Modality; Molecular Profiling; Monitor; Pathway interactions; Patients; Pharmaceutical Preparations; Phase; Physiological; Pilot Projects; Process; Property; Proteins; RNA; Reporting; Reverse Transcriptase Polymerase Chain Reaction; Risk; Role; Sampling; Severities; Signal Transduction; Site; Specificity; Stream; Structure; Surface; Surrogate Markers; Testing; Therapeutic; Time; Tissue Sample; Tissues; Ulcerative Colitis; Variant; Vesicle; Work; activity marker; base; cell type; chemokine; cohort; cost; cytokine; drug clearance; extracellular; intercellular communication; interest; microbial; microbiome; nano; nanoparticle; neoplastic cell; neutrophil; prospective; public health relevance; vesicular release

 DESCRIPTION (provided by applicant): Recent advances in cell biology have reported a role for extracellular vesicles (EVs) in cell-cell signaling. These are small 'packets' of cellular contnt (such as RNA) that can be shed from cells, and reflect the characteristics of the originating cells Studies in cancer have shown these EVs to be useful markers of neoplastic cells, and are a mechanism to clear cancer drugs and influence surrounding cells. Although their use as a signature of abnormal cell types is clinically interesting, the ability of EVs to influence the actvity of neighboring cells is of great potential significance in our understanding of disease processes. In inflammatory conditions, EVs released from local cells could have immune modulating, and drug clearance, properties. In patients with Inflammatory Bowel Disease (IBD), the underlying chronic intestinal inflammation exhibits variations in both location and severity over time. Contemporary means of monitoring disease activity are limited by costs, complications or specificity (e.g. CT, colonoscopy). Preliminary work from the applicant's K23-funded project has isolated EVs from the intestinal lumen of patients with active colitis. These cellular signaling vehicles preserve their RNA and protein content from degradation, making them suitable for detection in fecal samples. This application proposes to obtain intestinal fluid, fecal and tissue samples from patients with IBD, and healthy controls, to test them for the presence of EVs, and describe their characteristics based on content and surface markers. The study will compare levels, and content of, EVs isolated from the intestinal tract between patients with active and inactive disease as a disease activity comparator. It will also determine whether fecal samples reflect the content of EVs that are isolated from the intestinal lumen. In addition, this study wil measure the effect of these isolated EVs on intestinal epithelial cells in culture, to determine if they alter the gene expression patterns and chemotactic properties of these cells. This proposal would generate preliminary data to support further examining the role of luminal EVs as markers of disease activity, and mediators or inflammatory signals throughout the intestinal tract. The impact of secreted EVs on the composition and function of the intestinal microbiome is also planned in future studies.

 描述（由申请人提供）：细胞生物学的最新进展已经报道了细胞外囊泡（EV）在细胞-细胞信号传导中的作用。这些是可以从细胞中脱落的细胞成分（如RNA）的小“包”，并反映了起源细胞的特征。癌症研究表明，这些EV是肿瘤细胞的有用标志物，是清除癌症药物和影响周围细胞的机制。虽然它们作为异常细胞类型的特征在临床上是有趣的，但EV影响邻近细胞活性的能力在我们理解疾病过程中具有重要的潜在意义。在炎症条件下，从局部细胞释放的EV可能具有免疫调节和药物清除特性。 在患有炎症性肠病（IBD）的患者中，潜在的慢性肠道炎症随着时间的推移在位置和严重程度方面表现出变化。监测疾病活动的当代手段受到成本、并发症或特异性（例如CT、结肠镜检查）的限制。申请人的K23资助项目的初步工作已经从活动性结肠炎患者的肠腔中分离出EV。这些细胞信号载体保护其RNA和蛋白质含量不被降解，使其适合在粪便样品中检测。本申请提出从IBD患者和健康对照者获得肠液、粪便和组织样本，以测试它们是否存在EV，并基于内容物和表面标记物描述它们的特征。该研究将比较活动性和非活动性疾病患者之间从肠道分离的EV的水平和含量，作为疾病活动性比较。它还将确定粪便样本是否反映了从肠腔分离的EV的含量。此外，本研究将测量这些分离的EV对培养的肠上皮细胞的影响，以确定是否 它们改变这些细胞的基因表达模式和趋化特性。该提案将产生初步数据，以支持进一步研究管腔EV作为疾病活动标志物的作用，以及整个肠道的介质或炎症信号。分泌的EV对肠道微生物组的组成和功能的影响也计划在未来的研究中进行。