HIF-1 α is transcriptionally regulated by NF-κB in acute kidney injury

In this study, the mechanism of HIF-α regulation in AKI was investigated. We found that tubular HIF-1α expression significantly increased at the transcriptional level in ischemia/reperfusion (I/R)-, unilateral ureteral obstruction (UUO)-, and sepsis-induced AKI models, which was closely associated with macrophage-dependent inflammation. Meanwhile, nuclear factor-κB (NF-κB), which plays a central role in 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 in hypoxic condition, but also in normoxic condition. Moreover, the induced HIF-1α by inflammation protected against the tubular injury in AKI. Thus, our findings not only provide novel insight into HIF-1 regulation in AKI but also offer to understand the pathophysiology of kidney diseases.PMID:34229478 | DOI:10.1152/ajprenal.00119.2021

Source: Am J Physiol Renal P... - July 7, 2021 Category: Urology & Nephrology Authors: Zuo-Lin Li Jia-Ling Ji Yi Wen Jingyuan Cao Naresh Kharbuja Wei-Jie Ni Di Yin Song-Tao Feng Hong Liu Lin-Li Lv Bi-Cheng Liu Bin Wang Source Type: research