Departments of Nephrology and Physiology, Inner City Campus, University of Munich, Munich, Germany.
Curr Genomics. 2010 Dec;11(8):584-90. doi: 10.2174/138920210793360961.
Nuclear factor of activated T cells 5 (NFAT5) is the most recently described member of the Rel family of transcription factors, including NF-κB and NFAT1-4, which play central roles in inducible gene expression during the immune response. NFAT5 was initially described to drive osmoprotective gene expression in renal medullary cells, which are routinely faced by high extracellular osmolalities. Recent data however indicate profound biological importance of the mammalian osmotic stress response in view of NFAT5 dependent gene regulation in non-renal tissues. In mononuclear cells and epithelial cells, NFAT5 stimulates the expression of various pro-inflammatory cytokines during elevated ambient tonicity. Accordingly, compared to plasma, the interstitial tonicity of lymphoid organs like spleen and thymus and that of liver is substantially hypertonic under physiological conditions. In addition, anisotonic disorders (hypernatremia, diabetes mellitus, dehydration) entail systemic hyperosmolality, and, in inflammatory disorders, the skin, intestine, and cornea are sites of local hyperosmolality. This article summarizes the current knowledge regarding systemic and local osmotic stress in anisotonic and inflammatory disorders in view of NFAT5 activation and regulation, and NFAT5 dependent cytokine production.
活化 T 细胞核因子 5（NFAT5）是最近描述的 Rel 家族转录因子成员之一，包括 NF-κB 和 NFAT1-4，它们在免疫反应中的诱导基因表达中发挥核心作用。NFAT5 最初被描述为驱动肾髓质细胞中的渗透保护基因表达，而肾髓质细胞经常面临高细胞外渗透压。然而，最近的数据表明，哺乳动物渗透应激反应具有深远的生物学重要性，因为 NFAT5 依赖的基因调节在非肾组织中发生。在单核细胞和上皮细胞中，NFAT5 在环境渗透压升高时刺激各种促炎细胞因子的表达。因此，与血浆相比，脾和胸腺等淋巴器官的间质渗透压以及肝的间质渗透压在生理条件下明显偏高。此外，非等渗性疾病（高钠血症、糖尿病、脱水）会导致全身高渗血症，而在炎症性疾病中，皮肤、肠道和角膜是局部高渗血症的部位。本文综述了在非等渗性和炎症性疾病中，鉴于 NFAT5 的激活和调节以及 NFAT5 依赖性细胞因子产生，全身性和局部渗透应激的最新知识。
