Deletion of the Cl-/HCO3- exchanger pendrin downregulates calcium-absorbing proteins in the kidney and causes calcium wasting.

The epithelial calcium channel (ECaC) (TRPV5) and the Cl-/HCO3- exchanger pendrin (SLC26A4) are expressed on the apical membrane of tubular cells in the distal nephron and play essential roles in calcium re-absorption and bicarbonate secretion, respectively, in the kidney. A combination of functional and molecular biology techniques were employed to examine the role of pendrin deletion in calcium excretion. Here, we demonstrate that deletion of pendrin causes acidic urine [urine pH 4.9 in knockout (KO) versus 5.9 in wild-type (WT) mice, P<0.03)] and downregulates the calcium-absorbing molecules ECaC and Na/Ca exchanger in the kidney, as shown by northern hybridization, immunoblot analysis and/or immunofluorescent labeling. These changes were associated with a ∼100% increase in 24-h urine calcium excretion in pendrin null mice. Subjecting the pendrin WT and KO mice to oral bicarbonate loading for 12 days increased the urine pH to ∼8 in both genotypes, normalized the expression of ECaC and Na/Ca exchanger and reduced the urine calcium excretion in pendrin-null mice to levels comparable to WT mice. We suggest that pendrin dysfunction should be suspected and investigated in humans with an otherwise unexplained acidic urine and hypercalciuria.

Citation

Sharon Barone, Hassane Amlal, Jie Xu, Manoocher Soleimani. Deletion of the Cl-/HCO3- exchanger pendrin downregulates calcium-absorbing proteins in the kidney and causes calcium wasting. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2012 Apr;27(4):1368-79

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PMID: 21873623

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