PDF(Pubmed)
Abstract：
Kidney diseases pose a significant global health issue, frequently resulting in the gradual decline of renal function and eventually leading to end-stage renal failure. Abnormal iron metabolism and oxidative stress-mediated cellular dysfunction facilitates the advancement of kidney diseases. Iron homeostasis is strictly regulated in the body, and disturbance in this regulatory system results in abnormal iron accumulation or deficiency, both of which are associated with the pathogenesis of kidney diseases. Iron overload promotes the production of reactive oxygen species (ROS) through the Fenton reaction, resulting in oxidative damage to cellular molecules and impaired cellular function. Increased oxidative stress can also influence iron metabolism through upregulation of iron regulatory proteins and altering the expression and activity of key iron transport and storage proteins. This creates a harmful cycle in which abnormal iron metabolism and oxidative stress perpetuate each other, ultimately contributing to the advancement of kidney diseases. The crosstalk of iron metabolism and oxidative stress involves multiple signaling pathways, such as hypoxia-inducible factor (HIF) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways. This review delves into the functions and mechanisms of iron metabolism and oxidative stress, along with the intricate relationship between these two factors in the context of kidney diseases. Understanding the underlying mechanisms should help to identify potential therapeutic targets and develop novel and effective therapeutic strategies to combat the burden of kidney diseases.
摘要：
肾脏疾病是一个重要的全球健康问题。常导致肾功能逐渐下降，最终导致终末期肾衰竭。铁代谢异常和氧化应激介导的细胞功能障碍促进了肾脏疾病的发展。铁稳态在体内受到严格的调节，这种调节系统的紊乱导致铁的异常积累或缺乏，两者都与肾脏疾病的发病机制有关。铁过载通过Fenton反应促进活性氧（ROS）的产生，导致细胞分子氧化损伤和细胞功能受损。增加的氧化应激还可以通过上调铁调节蛋白和改变关键铁转运和储存蛋白的表达和活性来影响铁代谢。这产生了一个有害的循环，其中异常的铁代谢和氧化应激相互延续，最终有助于肾脏疾病的发展。铁代谢与氧化应激的交叉涉及多个信号通路,如缺氧诱导因子（HIF）和核因子红系2相关因子2（Nrf2）途径。本文综述了铁代谢和氧化应激的功能和机制。在肾脏疾病的背景下，这两个因素之间错综复杂的关系。了解潜在的机制应有助于确定潜在的治疗靶标，并开发新颖有效的治疗策略来对抗肾脏疾病的负担。
