Abstract: SA-OR47
Hyperoxia Exposure in Neonatal Period Is Associated with Decrease in HB-EGF Expression in Mice Kidneys
Session Information
- Assessing Disease Risk in Children: A Developmental Perspective
November 06, 2021 | Location: Simulive, Virtual Only
Abstract Time: 04:30 PM - 06:00 PM
Category: Pediatric Nephrology
- 1700 Pediatric Nephrology
Authors
- Sakaria, Rishika P., The University of Tennessee Health Science Center, Memphis, Tennessee, United States
- White, Catrina, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
- Abdelgawad, Ahmed, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
- Talati, Ajay J., The University of Tennessee Health Science Center, Memphis, Tennessee, United States
- Willis, Kent A., The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
- Bajwa, Amandeep, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
Background
Acute Kidney Injury (AKI) is common in preterm infants and may cause long-lasting renal damage. Hyperoxia exposure in the postnatal period has been linked to chronic kidney disease (CKD) in adulthood in survivors or preterm birth. The mechanism of hyperoxia-driven AKI in premature infants is not clearly understood. Activation of the epidermal growth factor receptor (EGFR) by EGF or heparin-binding EGF-like growth factor (HB-EGF) promote renal tubular proliferation and renal recovery in AKI. In contrast, activation of transcribing growth factor (TGF-a) signaling may lead to fibrosis and CKD. We hypothesize that hyperoxia exposure in neonatal mice leads to kidney injury via alteration in the expression of EGFR and its ligands.
Methods
Pups of C57BI/6J mice were exposed to hyperoxia (FiO2 0.85) and compared to littermate controls exposed to room air from postnatal days 3-10. One kidney from each pup was fixed in formalin and embedded in paraffin for histological analysis. The other kidney was snap frozen and RT-PCR was performed from the RNA isolated from this kidney.
Results
We analyzed renal tissues from 15 newborn mice (from 3 litters) exposed to hyperoxia and 5 mice (from 1 litter) exposed to normoxia. Relative mRNA levels of HB-EGF were significantly decreased in renal tissues of pups exposed to hyperoxia (mean:0.006 ± 0.001) compared to those exposed to normoxia (mean:0.012 ± 0.002) (p < 0.05). Both EGFR and TGF-a were not elevated in pups exposed to hyperoxia. Hyperoxia-exposed pups were also noted to have elevated a-SMA and fibronectin compared to the controls. TGF-β levels were also similar between exposed and non-exposed animals (Figure 1).
Conclusion
HB-EGF may contribute to hyperoxia-related renal injury in preterm neonates and may be a therapeutic target in these infants.
Figure 1: *p < 0.05; **p < 0.005.
Funding
- Other NIH Support