Acute kidney injury (AKI) is a common critical clinical disease that is characterized by a rapid decline in renal function and reduced urine output. Ischemia and hypoxia are dominant pathophysiological changes in AKI that are induced by many factors, and the role of the “master” regulator hypoxia-inducible factor-1α (HIF-1α) is well recognized in AKI-related studies. MicroRNAs have been found to act as critical regulators of AKI pathophysiological process. More studies now have reported mutual interactions between HIF-1α and microRNAs in AKI. Therefore, in this brief review, we look into the mutual regulatory mechanisms between HIF-1α and microRNAs and discuss their function in the process of AKI. Recent studies demonstrated that HIF-1α is involved in the regulation of multiple functional microRNAs in AKI, and in turn, the level of HIF-1α is regulated by specific microRNAs. However, the role of the interactions between HIF-1α and microRNAs in AKI are controversial, and whether interventions targeting relevant mechanisms could achieve clinical benefits is not clear. Much work remains to further explore the value of targeting the HIF-1α-microRNA pathway in AKI treatment.
Impact statement: At first, we have discussed the role of hypoxia-inducible factor-1α (HIF-1α) and microRNAs in the acute kidney injury (AKI) pathophysiology. Then we have summarized the interactions between HIF-1α and microRNAs reported by AKI-related studies and concluded their regulatory effects in AKI process. Finally, we have made a vision of HIF-1α/microRNAs pathway’s potential as the intervention target in AKI. The mini review provides a systematic understanding of the crosstalk between HIF-1α and microRNAs in AKI and their effects on AKI pathophysiology and treatment.
Keywords: Acute kidney injury; biomarkers; hypoxia; hypoxia-inducible factor-1α; ischemia; microRNAs.