Department of Pharmacology, University of Virginia, Charlottesville, Virginia, USA.
Am J Physiol Cell Physiol. 2012 Jan 1;302(1):C1-8. doi: 10.1152/ajpcell.00327.2011. Epub 2011 Oct 12.
Tonicity-responsive enhancer binding protein (TonEBP/nuclear factor of activated T-cells 5 [NFAT5]) is a Rel homology transcription factor classically known for its osmosensitive role in regulating cellular homeostasis during states of hypo- and hypertonic stress. A recently growing body of research indicates that TonEBP is not solely regulated by tonicity, but that it can be stimulated by various tonicity-independent mechanisms in both hypertonic and isotonic tissues. Physiological and pathophysiological stimuli such as cytokines, growth factors, receptor and integrin activation, contractile agonists, ions, and reactive oxygen species have been implicated in the positive regulation of TonEBP expression and activity in diverse cell types. These new data demonstrate that tonicity-independent stimulation of TonEBP is critical for tissue-specific functions like enhanced cell survival, migration, proliferation, vascular remodeling, carcinoma invasion, and angiogenesis. Continuing research will provide a better understanding as to how these and other alternative TonEBP stimuli regulate gene expression in both health and disease.
张力反应增强结合蛋白（TonEBP/激活 T 细胞核因子 5 [NFAT5]）是一种 Rel 同源转录因子，其经典作用是在低渗和高渗应激状态下调节细胞内稳态的渗透压敏感性。最近越来越多的研究表明，TonEBP 不仅受张力调节，而且在高渗和等渗组织中，还可以通过多种与张力无关的机制被刺激。生理和病理刺激，如细胞因子、生长因子、受体和整合素激活、收缩激动剂、离子和活性氧，已被牵连在多种细胞类型中 TonEBP 表达和活性的正向调节中。这些新数据表明，TonEBP 的非张力依赖性刺激对于组织特异性功能（如增强细胞存活、迁移、增殖、血管重塑、癌浸润和血管生成）至关重要。进一步的研究将更好地了解这些和其他替代 TonEBP 刺激如何在健康和疾病状态下调节基因表达。
