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J Am Soc Nephrol. January 1, 2017; 28 (1): 242-249.

Loss of Cystic Fibrosis Transmembrane Regulator Impairs Intestinal Oxalate Secretion.

Knauf F , Thomson RB , Heneghan JF , Jiang Z , Adebamiro A , Thomson CL , Barone C , Asplin JR , Egan ME , Alper SL , Aronson PS .

Patients with cystic fibrosis have an increased incidence of hyperoxaluria and calcium oxalate nephrolithiasis. Net intestinal absorption of dietary oxalate results from passive paracellular oxalate absorption as modified by oxalate back secretion mediated by the SLC26A6 oxalate transporter. We used mice deficient in the cystic fibrosis transmembrane conductance regulator gene (Cftr) to test the hypothesis that SLC26A6-mediated oxalate secretion is defective in cystic fibrosis. We mounted isolated intestinal tissue from C57BL/6 (wild-type) and Cftr(-/-) mice in Ussing chambers and measured transcellular secretion of [(14)C]oxalate. Intestinal tissue isolated from Cftr(-/-) mice exhibited significantly less transcellular oxalate secretion than intestinal tissue of wild-type mice. However, glucose absorption, another representative intestinal transport process, did not differ in Cftr(-/-) tissue. Compared with wild-type mice, Cftr(-/-) mice showed reduced expression of SLC26A6 in duodenum by immunofluorescence and Western blot analysis. Furthermore, coexpression of CFTR stimulated SLC26A6-mediated Cl(-)-oxalate exchange in Xenopus oocytes. In association with the profound defect in intestinal oxalate secretion, Cftr(-/-) mice had serum and urine oxalate levels 2.5-fold greater than those of wild-type mice. We conclude that defective intestinal oxalate secretion mediated by SLC26A6 may contribute to the hyperoxaluria observed in this mouse model of cystic fibrosis. Future studies are needed to address whether similar mechanisms contribute to the increased risk for calcium oxalate stone formation observed in patients with cystic fibrosis.

PubMed ID: 27313231
PMC ID: PMC5198290
Article link: J Am Soc Nephrol.
Grant support: P30 DK079310 NIDDK NIH HHS , R37 DK033793 NIDDK NIH HHS , R37 DK043495 NIDDK NIH HHS , T32 DK007760 NIDDK NIH HHS

External Resources:

Andrieux, 2010, Pubmed [+]

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