Back to Search
Start Over
HIF-1α is transcriptionally regulated by NF-κB in acute kidney injury.
- Source :
- American Journal of Physiology: Renal Physiology; Aug2021, Vol. 321 Issue 2, pF225-F235, 11p
- Publication Year :
- 2021
-
Abstract
- Oxygen homeostasis disturbances play a critical role in the pathogenesis of acute kidney injury (AKI). The transcription factor hypoxia-inducible factor-1 (HIF-1) is a master regulator of adaptive responses to hypoxia. Aside from posttranslational hydroxylation, the mechanism of HIF-1 regulation in AKI remains largely unclear. In this study, the mechanism of HIF-a regulation in AKI was investigated. We found that tubular HIF-1α expression significantly increased at the transcriptional level in ischemia-reperfusion-, unilateral ureteral obstruction-, and sepsis-induced AKI models, which was closely associated with macrophage-dependent inflammation. Meanwhile, NF-κB, which plays a central role in the inflammation response, was involved in the increasing expression of HIF-1α in AKI, as evidenced by pharmacological modulation (NF-κB inhibitor BAY11-7082). Mechanistically, NF-κB directly bound to the HIF-1α promoter and enhanced its transcription, which occurred not only under hypoxic conditions but also under normoxic conditions. Moreover, the induced HIF-1α by inflammation protected against tubular injury in AKI. Thus, our findings not only provide novel insights into HIF-1 regulation in AKI but also offer to understand the pathophysiology of kidney diseases. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 1931857X
- Volume :
- 321
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- American Journal of Physiology: Renal Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 152197548
- Full Text :
- https://doi.org/10.1152/ajprenal.00119.2021