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5-Lipoxygenase exerts dual and opposing functions during the wound healing process

5-脂氧合酶在伤口愈合过程中发挥双重和相反的功能

基本信息

批准号：
10456195
负责人：
Athena Soulika
金额：
$ 36.9万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-20 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10456195
关键词：
Affect Arachidonate 5-Lipoxygenase Arachidonic Acids Architecture Area Bulla Burn injury Caring Cell Proliferation Cells Chemotactic Factors Chemotaxis Complication Data Development Eicosanoids Enzymes Epithelial Exhibits Family G-Protein-Coupled Receptors Gene Expression Genes Genetic Hospital Costs Hospitalization Hypertrophic Cicatrix Impaired healing Impaired wound healing Impairment Infection Inflammation Inflammatory Inflammatory Response Injury Knockout Mice Lead Leukotriene B4 Leukotriene C4 Leukotriene D4 Leukotriene E4 Leukotriene Production Leukotrienes Liquid substance Mediating Mus Neutrophilic Infiltrate Normal tissue morphology Outcome Pathway interactions Patients Pattern Play Process Production Proteins Repeat Surgery Research Role Signal Transduction Site Skin Specificity Testing Tissues Tumor-infiltrating immune cells antagonist burn wound cell type cysteinyl-leukotriene design experimental study healing infection risk inflammatory milieu lipid mediator monocyte neovascularization neutrophil novel novel therapeutic intervention receptor-mediated signaling reconstruction repaired targeted treatment tissue reconstruction treatment strategy vasoconstriction wound wound healing

项目摘要

Despite significant advances in care, impaired healing after burn injury still remains a major concern. Impaired healing is associated with increased risk for infections and prolonged and costly hospitalization periods. Thus, delineation of specific mechanisms that govern wound healing is a dire objective in burn injury research. Here, we propose that activation of the 5-Lipoxygenase (5-LO) pathway at the affected site is a previously unappreciated mechanism that orchestraes burn wound healing. 5-LO mediates the synthesis of leukotrienes (LTs), a team of lipid mediators that derive from arachidonic acid. LTs consist of leukotriene B4 (LTB4) and the cysteinyl leukotrienes (cysLTs), and are all known for their proinflammatory functions. However, regulated LT activity may play roles in normal tissue function and repair. Our preliminary data show that the 5-LO pathway is active at the burn wound site. Interestingly our data suggest that LTB4 and cysLTs exert opposing functions in burn wound healing. This study is designed to dissect the mechanisms by which 5-LO activity orchestrates healing after burn injury. Furthermore, we will examine the hypothesis that heightened 5-LO/LTB4 activity at the wound site early after injury is associated with impaired healing in burn patients. Successful completion of this proposal will have implications on the development of new therapeutic strategies for patients with non-healing burn injuries.

尽管在护理方面取得了重大进展，但烧伤后愈合不良仍然是一个主要问题。受损愈合与感染的风险增加以及住院时间延长和费用昂贵有关。因此，在本发明中，描述控制伤口愈合的特定机制是烧伤研究中的一个可怕的目标。在这里，我们提出，激活5-脂氧合酶（5-LO）途径，在受影响的网站是一个先前的管弦乐队促进烧伤伤口愈合的不受重视的机制。5-LO介导白三烯的合成 (LTs)，一组来自花生四烯酸的脂质介质。LT由白三烯B4（LTB 4）和半胱氨酰白三烯（cysLT），并且都以其促炎功能而闻名。然而，受监管的LT 活性可能在正常组织功能和修复中起作用。我们的初步数据表明，5-LO途径是活跃的烧伤伤口部位。有趣的是，我们的数据显示， LTB 4和cysLTs在烧伤创面愈合中发挥相反的功能。这项研究旨在剖析 5-LO活性协调烧伤后愈合的机制。此外，我们将研究假设损伤后早期伤口部位5-LO/LTB 4活性升高与损伤相关，烧伤病人的康复成功完成这一提案将对新的治疗策略的发展产生影响对于无法愈合的烧伤患者。