Role of NFAT5 in inflammatory disorders associated with osmotic stress.
Role of NFAT5 in inflammatory disorders associated with osmotic stress.
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DOI：
10.2174/138920210793360961
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发表时间：
2010-12
期刊：
影响因子：
2.6
通讯作者：
Neuhofer W
中科院分区：
文献类型：
--
作者：
Neuhofer W
活化T细胞核因子5 （NFAT5）是Rel转录因子家族中最新发现的成员，包括NF-κB和NFAT1-4，在免疫应答过程中对诱导基因表达起核心作用。NFAT5最初被描述为驱动肾髓细胞中的渗透保护基因表达，肾髓细胞通常面临高细胞外渗透压。然而，最近的数据表明，鉴于NFAT5依赖基因在非肾组织中的调控，哺乳动物渗透应激反应具有深远的生物学意义。在单核细胞和上皮细胞中，NFAT5在环境张力升高时刺激各种促炎细胞因子的表达。因此，与血浆相比，在生理条件下，脾、胸腺等淋巴器官和肝脏的间质强直性实质上是高渗的。此外，各向异性疾病（高钠血症、糖尿病、脱水）会导致全身高渗，在炎症性疾病中，皮肤、肠道和角膜是局部高渗的部位。本文从NFAT5的激活和调控以及NFAT5依赖性细胞因子的产生等方面综述了目前关于各向异性和炎症性疾病的全身和局部渗透应激的知识。
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.