Renoprotective Role of Hypoxia-Inducible Factors and the Mechanism

Background: 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. Summary: 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. Key Messages: 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. (C) 2021 The Author(s). Published by S. Karger AG, Basel

Automated summary

HIFs accumulate and regulate target genes under hypoxia, maintaining homeostasis during injury; pretreatment of HIF can protect the kidney from acute hypoxia and improve repair, but HIF's role in CKD and renal tumors is controversial; due to its mechanism in kidney disease, drugs targeting HIFs are widely researched and some are in clinical use or clinical research.