HIF-1: a key mediator in hypoxia (Review)
HIF-1: a key mediator in hypoxia (Review)
复制标题
DOI：
10.1556/aphysiol.96.2009.1.2
复制
发表时间：
2009-03-01
影响因子：
--
通讯作者：
Nemeth, Z. H.
中科院分区：
文献类型：
--
作者：
Adams, J. M.;Difazio, L. T.;Nemeth, Z. H.
转录因子HIF-1是暴露于缺氧的人体组织中稳态的主要介质之一。它几乎涉及响应低氧水平的快速基因表达的每个过程。组织缺氧的最常见原因是炎症和/或循环不足或两者的组合。炎症组织和恶性肿瘤周围区域的特征是缺氧和低浓度的葡萄糖。严重和全身性炎症可导致败血症和循环衰竭，导致各种重要器官中的急性或慢性组织缺氧，这在人体中受影响器官的所有有核细胞中诱导快速稳态过程。在缺氧条件下，HIF-1的α和β亚基产生活性异源二聚体，并驱动超过60个基因的转录，这些基因对细胞存活、适应、无氧代谢、免疫反应、细胞因子产生、血管形成和一般组织稳态很重要。此外，HIF-1在胎儿和出生后的生理系统发育中起着关键作用。它也是癌症、肺和心血管疾病的关键介质。更好地理解HIF-1的功能及其活性的药理学调节可能意味着这些疾病的成功治疗方法。
The transcription factor HIF-1 is one of the principal mediators of homeostasis in human tissues exposed to hypoxia. It is implicated in virtually every process of rapid gene expression in response to low oxygen levels. The most common causes of tissue hypoxia are inflammation and/or insufficient circulation or a combination of both. Inflamed tissues and the areas surrounding malignant tumors are characterized by hypoxia and low concentrations of glucose. Serious and generalized inflammation can lead to sepsis and circulatory collapse resulting in acute or chronic tissue hypoxia in various vital organs which induces a rapid homeostatic process in all nucleated cells of affected organs in the human body. Under hypoxic conditions the alpha and beta subunits of HIF-1 make an active heterodimer and drive the transcription of over 60 genes important for cell survival, adaptation, anaerobic metabolism, immune reaction, cytokine production, vascularization and general tissue homeostasis. In addition, HIF-1 plays a key role in the development of physiological systems in fetal and postnatal life. It is also a critical mediator of cancer, lung and cardiovascular diseases. The better understanding of the functions of HIF-1 and the pharmacological modulation of its activity could mean a successful therapeutic approach to these diseases.