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J Am Soc Nephrol
2017 Jan 01;281:242-249. doi: 10.1681/ASN.2016030279.
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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
.
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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 [14C]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.
Andrieux,
Renal impairment in children with cystic fibrosis.
2010, Pubmed
Andrieux,
Renal impairment in children with cystic fibrosis.
2010,
Pubmed
Asplin,
The management of patients with enteric hyperoxaluria.
2016,
Pubmed
Assimos,
Re: Loss of Cystic Fibrosis Transmembrane Regulator Impairs Intestinal Oxalate Secretion.
2018,
Pubmed
Böhles,
Antibiotic treatment-induced tubular dysfunction as a risk factor for renal stone formation in cystic fibrosis.
2002,
Pubmed
Capolongo,
Subclinical celiac disease and crystal-induced kidney disease following kidney transplant.
2012,
Pubmed
Cartery,
Oxalate nephropathy associated with chronic pancreatitis.
2011,
Pubmed
Chernova,
Functional comparison of mouse slc26a6 anion exchanger with human SLC26A6 polypeptide variants: differences in anion selectivity, regulation, and electrogenicity.
2005,
Pubmed
,
Xenbase
Chidekel,
Cystic fibrosis and calcium oxalate nephrolithiasis.
1996,
Pubmed
Chou,
Acquired bartter-like syndrome associated with gentamicin administration.
2005,
Pubmed
Clark,
Species differences in Cl- affinity and in electrogenicity of SLC26A6-mediated oxalate/Cl- exchange correlate with the distinct human and mouse susceptibilities to nephrolithiasis.
2008,
Pubmed
,
Xenbase
Crites,
CFTR Knockdown induces proinflammatory changes in intestinal epithelial cells.
2015,
Pubmed
Cunningham,
cAMP-stimulated ion currents in Xenopus oocytes expressing CFTR cRNA.
1992,
Pubmed
,
Xenbase
Eckman,
Dietary changes improve survival of CFTR S489X homozygous mutant mouse.
1995,
Pubmed
Freel,
Ileal oxalate absorption and urinary oxalate excretion are enhanced in Slc26a6 null mice.
2006,
Pubmed
Freel,
Enteric oxalate secretion is not directly mediated by the human CFTR chloride channel.
2008,
Pubmed
,
Xenbase
Gibney,
The association of nephrolithiasis with cystic fibrosis.
2003,
Pubmed
Heneghan,
Regulated transport of sulfate and oxalate by SLC26A2/DTDST.
2010,
Pubmed
,
Xenbase
Hess,
High-calcium intake abolishes hyperoxaluria and reduces urinary crystallization during a 20-fold normal oxalate load in humans.
1998,
Pubmed
Holmes,
Dietary oxalate loads and renal oxalate handling.
2005,
Pubmed
Hoppe,
Absorptive hyperoxaluria leads to an increased risk for urolithiasis or nephrocalcinosis in cystic fibrosis.
2005,
Pubmed
Jiang,
Specificity of anion exchange mediated by mouse Slc26a6.
2002,
Pubmed
,
Xenbase
Jiang,
Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6.
2006,
Pubmed
Knauf,
NALP3-mediated inflammation is a principal cause of progressive renal failure in oxalate nephropathy.
2013,
Pubmed
Knauf,
Net intestinal transport of oxalate reflects passive absorption and SLC26A6-mediated secretion.
2011,
Pubmed
Ko,
Gating of CFTR by the STAS domain of SLC26 transporters.
2004,
Pubmed
Ko,
Sat1 is dispensable for active oxalate secretion in mouse duodenum.
2012,
Pubmed
Ko,
A molecular mechanism for aberrant CFTR-dependent HCO(3)(-) transport in cystic fibrosis.
2002,
Pubmed
Lohi,
Isoforms of SLC26A6 mediate anion transport and have functional PDZ interaction domains.
2003,
Pubmed
,
Xenbase
MacKenzie,
Longevity of patients with cystic fibrosis in 2000 to 2010 and beyond: survival analysis of the Cystic Fibrosis Foundation patient registry.
2014,
Pubmed
Matthews,
Urolithiasis and cystic fibrosis.
1996,
Pubmed
Norkina,
Inflammation of the cystic fibrosis mouse small intestine.
2004,
Pubmed
Ozçelik,
Hypercalciuria and nephrocalcinosis in cystic fibrosis patients.
2004,
Pubmed
Perez-Brayfield,
Metabolic risk factors for stone formation in patients with cystic fibrosis.
2002,
Pubmed
Raia,
Evidence of chronic inflammation in morphologically normal small intestine of cystic fibrosis patients.
2000,
Pubmed
Snouwaert,
An animal model for cystic fibrosis made by gene targeting.
1992,
Pubmed
Thomson,
Role of PDZK1 in membrane expression of renal brush border ion exchangers.
2005,
Pubmed
Tuo,
Involvement of phosphatidylinositol 3-kinase in cAMP- and cGMP-induced duodenal epithelial CFTR activation in mice.
2009,
Pubmed
Wright,
Biology of human sodium glucose transporters.
2011,
Pubmed
