Li Qiu-Yu, Liu Fei, Tang Xiaoxiao, Fu Haidong, Mao Jianhua
Department of Nephrology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, China.
Kidney Dis (Basel). 2021 Nov 23;8(1):44-56. doi: 10.1159/000520141. eCollection 2022 Jan.
The kidney requires abundant blood supply, and oxygen is transmitted by diffusion through blood vessels. Most physiological metabolism of the kidney depends on oxygen, so it is very sensitive to oxygen. An increasing pool of evidence suggests that hypoxia is involved in almost all acute and chronic kidney diseases (CKDs). Vascular damage, tubular injury, and fibrosis are the main pathologies associated during hypoxia. Hypoxia-inducible factors (HIFs) are the main mediators during hypoxia, but their functions remain controversial. This article reviewed recent studies and described its mechanisms on renoprotection.
HIF is degraded rapidly during under normal oxygen. But under hypoxia, HIFs accumulate and many target genes are regulated by HIFs. Homeostasis during injury is maintained through these genes. Pretreatment of HIF can protect the kidney from acute hypoxia and can improve repair, but HIF's role in CKD and in renal tumor is still controversial. Due to its mechanism in kidney disease, many drugs toward HIFs are widely researched, even some of which have been used in clinical or in clinical research.
In this review, we described the known physiological mechanisms, target genes, and renal protective roles of HIFs, and we discussed several drugs that are researched due to such renal protective roles.
肾脏需要丰富的血液供应，氧气通过血管扩散进行传输。肾脏的大多数生理代谢都依赖氧气，因此对氧气非常敏感。越来越多的证据表明，缺氧几乎涉及所有急性和慢性肾脏病（CKD）。血管损伤、肾小管损伤和纤维化是缺氧期间相关的主要病理变化。缺氧诱导因子（HIFs）是缺氧期间的主要介质，但其功能仍存在争议。本文综述了近期研究并描述了其肾脏保护机制。
在正常氧环境下，HIF会迅速降解。但在缺氧状态下，HIFs会积累，许多靶基因受HIFs调控。通过这些基因维持损伤期间的内环境稳定。HIF预处理可保护肾脏免受急性缺氧影响并促进修复，但HIF在CKD和肾肿瘤中的作用仍存在争议。由于其在肾脏疾病中的作用机制，许多针对HIFs的药物正在广泛研究中，甚至有些已用于临床或临床研究。
在本综述中，我们描述了HIFs已知的生理机制、靶基因和肾脏保护作用，并讨论了因这种肾脏保护作用而正在研究的几种药物。
