| First Author | Barone S | Year | 2012 |
| Journal | Nephrol Dial Transplant | Volume | 27 |
| Issue | 4 | Pages | 1368-79 |
| PubMed ID | 21873623 | Mgi Jnum | J:329170 |
| Mgi Id | MGI:7341755 | Doi | 10.1093/ndt/gfr505 |
| Citation | Barone S, et al. (2012) Deletion of the Cl-/HCO3- exchanger pendrin downregulates calcium-absorbing proteins in the kidney and causes calcium wasting. Nephrol Dial Transplant 27(4):1368-79 |
| abstractText | BACKGROUND: 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. METHODS: A combination of functional and molecular biology techniques were employed to examine the role of pendrin deletion in calcium excretion. RESULTS: 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 approximately 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 approximately 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. CONCLUSIONS: We suggest that pendrin dysfunction should be suspected and investigated in humans with an otherwise unexplained acidic urine and hypercalciuria. |
