Kidney Week

Abstract: TH-PO496

Transcriptome Profiling in Pendrin Deficient Mice Provides New Insight into the Role of Pendrin in Kidney Physiology

Session Information

• Fluid and Electrolytes: Basic - I
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid and Electrolytes

• 901 Fluid and Electrolytes: Basic

Authors

• Xu, Jie, University of Cincinnati, Cincinnati, Ohio, United States

Jie Xu,

• Barone, Sharon L., University of Cincinnati, Cincinnati, Ohio, United States

Sharon L. Barone,

• Zahedi, Kamyar A., University of Cincinnati, Cincinnati, Ohio, United States

Kamyar A. Zahedi,

• Soleimani, Manoocher, University of Cincinnati, Cincinnati, Ohio, United States

Manoocher Soleimani,

Background

Slc26a4 (Pendrin) is a Cl^-/HCO₃^- exchanger that is primarily expressed on the apical membrane of B-intercalated cells in the kidney connecting tubules/cortical collecting ducts and plays a critical role in salt absorption and bicarbonate secretion.

Methods

To gain better insight into the role of pendrin in kidney function, RNA-Seq analysis was performed on kidney cortices of wild type and pendrin KO mice and results verified by Northern hybridization and/or immunofluorescence labeling.

Results

The most dramatic changes in the expression of solute transporters belonged to the families of organic anion and cation transporters and their collaborating partners, which are primarily expressed in the proximal tubule. The expression of the basolateral organic anion transporters, OAT1 and OAT3 (Slc22a6 and a8), along with their interacting partner NaDC-3 (Slc13a3), was significantly increased and paralleled a robust enhancement in the expression of the apical voltage driven urate efflux transporter Npt4 (Slc17a3).
Likewise, the expression of the basolateral organic cation transporter, Oct2 (Slc22a2) increased and was matched by the enhanced expression of MATE1 (SLC47A1) and NHE-8 (Slc9a8) on the apical membrane. The activation of NHE-8 is likely to provide the necessary luminal proton for MATE1, an organic cation/H⁺ exchanger on the apical membrane of the proximal tubule. In addition, the Na⁺-Sulfate cotransporter (Slc13a1) which is expressed on the apical membrane of proximal tubules and mediates sulfate absorption showed significant up-regulation.

Conclusion

In conclusion, deletion of Slc26a4 is associated with enhanced expression of organic anion and cation transporters on the basolateral and apical membranes of the proximal tubule. We propose that the coordinated regulation of organic anion and cation transporters in the kidney proximal tubule of pendrin KO mice supports an important role for pendrin in the excretion of endogenous and exogenous organic cations (such as creatinine, guanidine, metformin, cisplatinum, etc), endogenous and exogenous organic anions (uric acid, prostaglandins, uremic toxins, penicillin, methotrexate, linezolid, etc ), and inorganic anions such as sulfate.

Funding

• Veterans Affairs Support