Effect of redox modulating NRF2 activators on chronic kidney disease.
Effect of redox modulating NRF2 activators on chronic kidney disease.
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DOI：
10.3390/molecules190812727
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发表时间：
2014-08-20
期刊：
影响因子：
--
通讯作者：
Kwak MK
中科院分区：
文献类型：
--
作者：
Choi BH;Kang KS;Kwak MK
慢性肾病（Chronic kidney disease， CKD）是以肾功能进行性下降为特征的疾病，主要由糖尿病、高血压等慢性疾病引起。CKD是一种复杂的疾病，由于心血管并发症和高发病率；然而，没有单一的治疗方法可以改善CKD患者的肾功能。由于代表氧化应激的生物标志物在CKD患者中显著升高，氧化应激作为CKD病理的一个促进因素正在受到关注。核因子-红细胞-2相关因子2 （NRF2）是一种主要的转录因子，它调节一系列基因的表达，这些基因编码抗氧化蛋白、硫醇分子及其生成酶、解毒酶和应激反应蛋白，所有这些基因都可以抵消炎症和氧化损伤。大量实验证据表明NRF2信号在各种病理条件引起的肾损伤中起保护作用。此外，在CKD动物中观察到NRF2活性受损和随之而来的靶基因抑制。因此，激活NRF2信号的药物干预可能有助于预防CKD患者的肾功能障碍。这篇综述文章概述了NRF2在实验性CKD模型中的作用，并描述了天然NRF2激活剂（包括萝卜硫素、白藜芦醇、姜黄素和肉桂醛）对肾脏保护作用的最新发现。这些实验结果，加上最近合成的三萜，甲基巴多洛酮的临床经验，为通过防止氧化应激和维持细胞氧化还原稳态来改善CKD进展带来了希望。
Chronic kidney disease (CKD) is featured by a progressive decline of kidney function and is mainly caused by chronic diseases such as diabetes mellitus and hypertension. CKD is a complex disease due to cardiovascular complications and high morbidity; however, there is no single treatment to improve kidney function in CKD patients. Since biological markers representing oxidative stress are significantly elevated in CKD patients, oxidative stress is receiving attention as a contributing factor to CKD pathology. Nuclear factor erythroid-2 related factor 2 (NRF2) is a predominant transcription factor that regulates the expression of a wide array of genes encoding antioxidant proteins, thiol molecules and their generating enzymes, detoxifying enzymes, and stress response proteins, all of which can counteract inflammatory and oxidative damages. There is considerable experimental evidence suggesting that NRF2 signaling plays a protective role in renal injuries that are caused by various pathologic conditions. In addition, impaired NRF2 activity and consequent target gene repression have been observed in CKD animals. Therefore, a pharmacological intervention activating NRF2 signaling can be beneficial in protecting against kidney dysfunction in CKD. This review article provides an overview of the role of NRF2 in experimental CKD models and describes current findings on the renoprotective effects of naturally occurring NRF2 activators, including sulforaphane, resveratrol, curcumin, and cinnamic aldehyde. These experimental results, coupled with recent clinical experiences with a synthetic triterpenoid, bardoxolone methyl, have brought a light of hope for ameliorating CKD progression by preventing oxidative stress and maintaining cellular redox homeostasis.
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