通过TSG6氨酸基基质的重塑,可以减轻大肠炎期间的炎症反应
Nansy Albtoush1, Kimberly A Queisser1, Ash Zawerton2
1University of Utah Molecular Medicine Program, Salt Lake City, Utah, 84112; Lerner Research Institute, Department of Inflammation & Immunity, Cleveland Clinic, Cleveland, OH 44195, USA.
瘤亡因子刺激基因-6 (TSG6) 修改氨酸 (HA) 形成保护性复合体,减少炎症性肠病 (IBD) 中的炎症. 失去TSG6功能会通过破坏HA矩阵和增加免疫细胞透来恶化结肠炎.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 细胞外矩阵生物学 细胞外矩阵生物学
背景情况:
- 细胞外基质 (ECM) 的变化会影响炎症反应和疾病进展.
- 氨酸 (HA) 在炎症期间被瘤亡因子刺激基因-6 (TSG6) 改变,形成重链 (HC):HA复合体.
- 炎症性肠病 (IBD) 涉及ECM重塑和白细胞透,HC:HA矩阵沉积之前免疫细胞的涌入.
研究的目的:
- 调查TSG6在结肠炎模型中的炎症反应中的作用和酶活性.
- 了解HA矩阵的TSG6-介导修改如何影响肠道炎症和免疫细胞行为.
主要方法:
- 从IBD患者和对照对象的炎症组织中分析TSG6和HA水平.
- 在TSG6缺乏的小鼠中评估急性结肠炎的严重程度和免疫反应.
- 抑制TSG6的重链 (HC) 转移酶活性,并评估其对HA稳定性和白细胞粘附的影响.
- 生物化学生成HC:HA复合体,并评估它们对激活单细胞炎症反应的影响.
主要成果:
- IBD患者的结肠组织呈现高TSG6和HC沉积,HA水平与TSG6有很强的相关性.
- 缺乏TSG6的小鼠对急性结肠炎的敏感性增加,其特征是炎症性细胞因子/化学因子的增加和IL-10的减少.
- 缺少TSG6会导致HA矩阵的混乱和组织HA水平的降低.
- 抑制TSG6HC转移酶活动会破坏细胞表面HA和白细胞粘附.
- 来自TSG6的HC:HA复合体减弱了激活单细胞的炎症反应.
结论:
- TSG6通过产生HC:HA复合体在肠道中发挥着关键的组织保护和抗炎作用.
- TSG6及其产生的HC:HA复合体的失调有助于炎症性肠病 (IBD) 的病理.
- 在炎症期间,TSG6的酶活性对于维持HA ECM稳定性至关重要.
更多相关视频
09:11Systematic Scoring Analysis for Intestinal Inflammation in a Murine Dextran Sodium Sulfate-Induced Colitis Model
Published on: February 14, 2021
10:21Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
Published on: September 12, 2019
相关概念视频
Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
TGF - β Signaling Pathway
Inflammatory Response II: Inflammatory Exudate and Tissue Repair
The typical wound exudate is odorless, transparent, straw-colored, thin, and watery. Exudate, however, can differ depending on the state of wound healing. Likewise, the...
Inflammatory Bowel Disease II: Crohn's Disease
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
