Abstract: PO1103
Deletion of the EP3 Receptor in the Kidney Tubule of Adult Mice Has No Impact on the Major Channels and Transporters Involved in Kidney Water Handling
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Basic
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid, Electrolyte, and Acid-Base Disorders
- 901 Fluid, Electrolyte, and Acid-Base Disorders: Basic
Authors
- Esteva-Font, Cristina, Aarhus Universitet, Aarhus, Midtjylland, Denmark
- Geurts, Frank, Erasmus MC, Rotterdam, Netherlands
- Hoorn, Ewout J., Erasmus MC, Rotterdam, Netherlands
- Fenton, Robert A., Aarhus Universitet, Aarhus, Midtjylland, Denmark
Background
Prostaglandin E2 (PGE2) is an important lipid mediator modulating various aspects of kidney function. PGE2 exerts its effects via four PGE2 receptors, EP1-EP4, but it is unclear which PGE2 effects are mediated through which receptor. The EP3 receptor is expressed in the thick ascending limb (TAL) and the collecting duct, where it is proposed to inhibit cAMP generation and NaCl and water reabsorption. However, EP3 is also expressed in endothelial cells of arteries and arterioles, that also play a role in kidney function.
Methods
To assess the tubular role of EP3 in adult mice we generated a mouse model based on the Pax8Cre system with doxycycline-dependent deletion of EP3 along the renal tubule and assessed their renal phenotype in respect to water handling. qPCR and RNAscope confirmed that EP3 was highly expressed in cortical and medullary TAL and collecting ducts, but it was not detected in proximal tubule and thin limbs.
Results
Two weeks after treatment with doxycycline, EP3 mRNA expression was reduced by >80% in whole kidney (RT-q-PCR) and non-detectable (RNAscope) in tubules of knockout mice compared to control mice. The other EP receptors expression remained unchanged in the kidney except for a slightly increase in EP4 expression. Under basal conditions, there were no significant differences in food and water intake, bodyweight, urinary output or plasma and urine biochemistries in both male and female control and knockout mice. There were no differences between genotypes in their kidney handling of water during an acute water load, or in their response to the vasopressin V2 receptor agonist dDAVP. Moreover, the expression levels of the main channels and transporters involved in kidney water handling, including AQP2, AQP3, AQP4, NKCC2, αENaC, UT-A1, ROMK and NaK-ATPase remained similar to the control mice.
Conclusion
This new model provides a novel tool for examination of the role of EP3 in other aspects of kidney function or kidney disease independently of potential developmental abnormalities or systemic effects.