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

缺氧诱导因子1（Hypoxia inducible factor 1，HIF-1）是缺氧组织适应缺氧的关键转录调节因子。HIF-1调控的基因包括铁和能量代谢、血管紧张素、血管发育和重塑以及血液的氧容量。除了缺氧，从受损组织释放的介质，即反应性O2-和N2-物质和细胞因子，可以激活HIF-1。在动物模型以及细胞培养研究中，将研究缺氧/复氧以及上述非缺氧刺激对HIF-1活化的程度和机制。通过体内2-光子和1-光子多焦点激光显微镜，创伤后相对于HIF-1靶基因的组织反应将被监测，并通过局部组成型活性HIF-1过表达进行修饰。在具有组织特异性HIF-1敲除的小鼠中，将研究缺乏HIF-1的后果。通过与SPP 1151的其他合作伙伴密切合作，我们的研究将包括创伤的潜在介质以及患者的组织标本。我们对HIF-1在机械性肌肉创伤中的作用的研究结果可以为严重创伤后组织修复的新治疗概念提供基础。

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.