The cytoprotective transcription factor NRF2 regulates the expression of several hundred genes in mammalian cells and is a promising therapeutic target in a number of diseases associated with oxidative stress and inflammation. Hence, an ability to monitor basal and inducible NRF2 signalling is vital for mechanistic understanding in translational studies. Due to some caveats related to the direct measurement of NRF2 levels, the modulation of NRF2 activity is typically determined by measuring changes in the expression of one or more of its target genes and/or the associated protein products. However, there is a lack of consensus regarding the most relevant set of these genes/proteins that best represents NRF2 activity across cell types and species. We present the findings of a comprehensive literature search that according to stringent criteria identifies GCLC, GCLM, HMOX1, NQO1, SRXN1 and TXNRD1 as a robust panel of markers that are directly regulated by NRF2 in multiple cell and tissue types. We assess the relevance of these markers in clinically accessible biofluids and highlight future challenges in the development and use of NRF2 biomarkers in humans.

中文翻译：

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NRF2 信号传导的生物标志物：现状和未来的挑战


细胞保护性转录因子 NRF2 调节哺乳动物细胞中数百个基因的表达，是许多与氧化应激和炎症相关疾病的有前景的治疗靶点。因此，监测基础和诱导型 NRF2 信号传导的能力对于转化研究中的机制理解至关重要。由于与直接测量 NRF2 水平相关的一些注意事项，NRF2 活性的调节通常通过测量一种或多种其靶基因和/或相关蛋白质产物的表达变化来确定。然而，对于这些基因/蛋白质中最相关的一组最能代表跨细胞类型和物种的 NRF2 活性缺乏共识。我们提出了全面文献检索的结果，根据严格的标准，将 GCLC、GCLM、HMOX1、NQO1、SRXN1 和 TXNRD1 确定为一组强大的标记物，在多种细胞和组织类型中受 NRF2 直接调节。我们评估了这些标记物在临床可利用的生物流体中的相关性，并强调了 NRF2 生物标记物在人类中的开发和使用的未来挑战。