Preoperative exercise therapy modulates neutrophil extracellular trap formation

术前运动疗法调节中性粒细胞胞外陷阱的形成

• 批准号: 10810353
• 负责人: Hai Huang
• 金额: $ 1.15万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-16 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10810353
• 关键词: Abdomen; Administrative Supplement; Anti-Inflammatory Agents; Award; Biogenesis; Biomedical Research; Cells; Development; Energy Metabolism; Environment; Excision; Exercise; Exercise Therapy; Foundations; Goals; Hepatic; Immune response; Immunity; Inflammation; Inflammatory; Inflammatory Response; Injury; Knowledge; Kupffer Cells; Liver; Macrophage; Medical Research; Mentors; Metabolic; Mitochondria; Morbidity - disease rate; Neutrophil Infiltration; Operative Surgical Procedures; Parents; Patients; Phenotype; Play; Postoperative Complications; Postoperative Period; Process; Recovery; Reperfusion Injury; Reperfusion Therapy; Research; Role; Serum; Stress; Training; Transaminases; career; chemokine; cost; cytokine; experience; extracellular; inflammatory milieu; innate immune function; ischemic injury; liver injury; liver ischemia; liver transplantation; mortality; neutrophil; novel; organ injury; parent grant; pharmacologic; prevent; programs; summer research; surgery outcome; systemic inflammatory response; therapeutic target; transcriptomics; undergraduate student

PROJECT DESCRIPTION: The goal of this Administrative Supplement application is to support an undergraduate student to obtain the authentic research experience during this summer by determining the mechanism by which preoperative exercise therapy modulates the capability of neutrophils forming neutrophil extracellular traps (NETs), which is highly relevant to the parent grant (R01GM137203) entitled "Preoperative exercise therapy for surgery triggered inflammation". Liver ischemia and reperfusion (I/R) is an unavoidable consequence of major liver resection and liver transplantation that leads to significant morbidity, mortality, and costs after liver surgery. However, previous strategies to protect the liver from I/R injury have focused on one specific known injury mechanisms, leaving intact other detrimental processes. Pre/post-operative exercise facilitates recovery after major abdominal surgery. It is known that exercise confers beneficial effects on the surgical outcome by regulating multiple mechanisms, including alteration of quantity and function of innate immune cells to provide an anti-inflammatory environment. We have discovered that preoperative exercise therapy (PET) significantly reduced serum aminotransferase levels (liver damage) and expression of cytokines and chemokines (inflammatory responses) during liver I/R via metabolic reprogramming Kupffer cells from pro- inflammatory to ani-inflammatory phenotype. However, even though cellular energy metabolism and mitochondrial biogenesis play a critical role in the immune response, the effects of PET-induced changes in neutrophils forming neutrophil extracellular traps (NETs) have never been studied. The undergraduate summer research program at Feinstein Institutes for Medical Research is a well-established research program that support undergraduate students who are considering pursuing biomedical research careers in cutting-edge scientific environments during the summer. Our proposed studies which will be conducted by undergraduate student will significantly expand the scope of the parent R01 award by interrogating two new questions related to those already being investigated in the parent R01 award: 1) What is the role of PET in the transcriptomic changes of infiltrating neutrophils after liver I/R? 2) Do PET-trained KCs suppress NET formation during liver I/R? In summary, the mentored studies that performed by undergraduate student in the Summer Research Program will significantly expand the current understanding of the underlying mechanistic mechanisms by which PET prevent surgical stress-induced organ injury via modulating NET formation and evaluate novel potential therapeutic targets, and assess promising novel treatments for patients undergoing surgery.

项目描述：本行政补充申请的目标是支持 本科生获得真实的研究经验，在今年夏天通过确定 术前运动疗法调节中性粒细胞形成中性粒细胞能力的机制 细胞外陷阱（NET），这是高度相关的母基金（R 01 GM 137203），题为“术前 手术运动疗法引发炎症”。肝脏缺血再灌注（I/R）是一种不可避免的 主要肝切除术和肝移植的后果，导致显著的发病率，死亡率， 肝脏手术后的费用然而，以前的策略，以保护肝脏从I/R损伤集中在一个 特定的已知损伤机制，留下完整的其他有害过程。术前/术后锻炼 有助于腹部大手术后的恢复。众所周知，锻炼对身体健康有有益的影响。 通过调节多种机制，包括先天性巨噬细胞数量和功能的改变， 免疫细胞来提供抗炎环境。我们发现术前锻炼 治疗（PET）显著降低血清转氨酶水平（肝损伤）和细胞因子表达 和趋化因子（炎症反应）在肝脏I/R通过代谢重编程枯否细胞从原- 炎性到非炎性表型。然而，即使细胞能量代谢和 线粒体生物合成在免疫应答中起着关键作用，PET诱导的线粒体生物合成的变化对免疫应答的影响， 形成中性粒细胞胞外陷阱（NET）的中性粒细胞从未被研究过。本科生的暑假 范斯坦医学研究所的研究项目是一个完善的研究项目， 支持正在考虑从事尖端生物医学研究职业的本科生 夏季的科学环境我们建议的研究将由本科生进行 学生将通过询问两个新的问题，大大扩大了父母R 01奖的范围 对于那些已经在父母R 01奖研究：1）PET在转录组学中的作用是什么？ 肝脏I/R后浸润中性粒细胞的变化？2)PET训练的KC是否抑制肝脏中的NET形成 I/R？总之，本科生在夏季研究中进行的指导研究 该计划将通过以下方式显着扩展当前对潜在机械机制的理解 其中PET通过调节NET形成来预防手术应激诱导的器官损伤，并评估新的 潜在的治疗靶点，并评估有前途的新的治疗方法，为患者接受手术。