Mechanisms and meaning of activation of Hypoxia-Inducible-Factor-1 (HIF-1) in muscle after mechanical trauma

机械创伤后肌肉缺氧诱导因子1（HIF-1）激活的机制及意义

• 批准号: 5408333
• 负责人: Professor Dr. Joachim Fandrey
• 金额: --
• 依托单位: Institut für Physiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2003
• 资助国家: 德国
• 起止时间: 2002-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5408333?language=en
• 关键词: Mechanisms; meaning; activation; Hypoxia; Inducible

Hypoxia inducible factor 1 (HIF-1) is the key regulatory transcription factor that ensures adequate adaptation of hypoxic tissue to the shortage of oxygen. HIF-1 regulated genes cover iron and energy metabolism, vasomotor tone, vascular development and remodeling and oxygen capacity of the blood. In addition to hypoxia, mediators released from damaged tissue, i.e. reactive O2- and N2-species and cytokines, can activate HIF-1. In an animal model as well as cell culture studies the extent and the mechanisms of HIF-1 activation by hypoxia/reoxygenation as well as the above mentioned non-hypoxic stimuli will be investigated. By in vivo 2-photon and 1-photon multifocal laser microscopy the tissue response after trauma with respect to HIF-1 target genes will be monitored and modified by local constitutively active HIF-1 overexpression. In mice with a tissue specific HIF-1 knock-out consequences of the lack of HIF-1 will be studied. In close cooperation with other partners of the SPP 1151 specifically potential mediators of trauma as well as tissue specimen from patients will be included in our study. Our findings on the role of HIF-1 in mechanical muscle trauma could provide the basis for new therapeutic concepts of tissue repair after severe trauma.

缺氧诱导因子 1 (HIF-1) 是确保缺氧组织充分适应缺氧的关键调控转录因子。 HIF-1调节的基因涵盖铁和能量代谢、血管舒缩张力、血管发育和重塑以及血液的氧容量。除了缺氧之外，受损组织释放的介质，即反应性 O2 和 N2 物质以及细胞因子，也可以激活 HIF-1。在动物模型和细胞培养研究中，将研究缺氧/复氧以及上述非缺氧刺激引起的 HIF-1 激活的程度和机制。通过体内 2 光子和 1 光子多焦点激光显微镜，将监测创伤后组织对 HIF-1 靶基因的反应，并通过局部组成性活性 HIF-1 过表达进行修改。将在具有组织特异性 HIF-1 敲除的小鼠中研究缺乏 HIF-1 的后果。我们与 SPP 1151 的其他合作伙伴密切合作，特别是潜在的创伤介质以及来自患者的组织标本将被纳入我们的研究中。我们关于 HIF-1 在机械性肌肉创伤中作用的发现可以为严重创伤后组织修复的新治疗概念提供基础。