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Kidney Week

Abstract: TH-PO121

High Oxygen Exposure Activates the Renal Endothelin System and Induces Extracellular Matrix Deposition

Session Information

  • AKI: Mechanisms - I
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Kraus, Abigayle, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Biswal, Sara, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • De Miguel, Carmen, University of Alabama at Birmingham, Birmingham, Alabama, United States

High oxygen supplementation is abundantly used in the clinical setting. Despite increasing evidence of excessive O2 increasing mortality and morbidity in ICU patients, the exact molecular mechanisms involved remain obscure. Of note, acute kidney injury and acute lung injury often occur in tandem in critical care and are both associated with elevated levels of endothelin-1 (ET-1) and ETA receptor overactivation. However, if the ET-1 system plays a role in kidney injury during exposure to elevated O2 levels remains unknown. These studies aimed to define the role of the ET-1 system in hyperoxia-induced kidney damage.


Male and female adult C57Bl/6N mice were exposed to room air (RA) or hyperoxia (HA, >95% O2) for 72 hours. Kidneys were collected for assessment of extracellular matrix deposition (ECM) via Picrosirius staining as well as mRNA expression of ET-1, and ETA and ETB receptors and ECM deposition markers in different kidney regions.


Kidneys from mice exposed to high O2 expressed significantly greater ET-1 levels compared to room air littermates. In response to HA, the outer and inner medulla showed a 2.3- and 5-fold upregulation of ET-1 mRNA expression, respectively (RA vs. HA, outer medulla: 1±0.23 vs. 2.3±0.35, p=0.02, n=6-8/group; inner medulla: 1±0.19 vs. 5.2±0.71, p=0.001), but no difference was observed in cortex (p=0.37). No differences in renal expression of ETA or ETB receptors were detected with HA. The HA-induced changes in the ET-1 system were accompanied by prominent ECM deposition in all areas of the kidney when visualized under bright-field and polarized light microscopy. Further, the inner medulla revealed a 4.5 fold increase in collagen IV gene expression when exposed to HA (1±0.40 vs. 4.01±1.00, p=0.02). No sex differences in the effects of HA on the kidney ET-1 system were detected.


In conclusion, high O2 exposure induces ECM deposition in the kidney and upregulates the ET-1 system, specifically in the renal medulla. Our findings strongly suggest that high O2 supplementation results in ET-1-mediated kidney injury. A better understanding of the renal ET-1 system response in high O2 states will help designing better pharmaceutical or O2 management interventions to limit the detrimental effects of high O2 supplementation and improve patient care.


  • Other NIH Support