{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T07:42:13Z","timestamp":1782891733515,"version":"3.54.5"},"reference-count":62,"publisher":"Walter de Gruyter GmbH","issue":"4","license":[{"start":{"date-parts":[[2018,12,1]],"date-time":"2018-12-01T00:00:00Z","timestamp":1543622400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chloride\/formate exchanger (CFEX; SLC26A6) mediates oxalate transport in various mammalian organs. Studies in Cfex knockout mice indicated its possible role in development of male-dominant hyperoxaluria and oxalate urolithiasis. Rats provide an important model for studying this pathophysiological condition, but data on Cfex (rCfex) localisation and regulation in their organs are limited. Here we applied the RT-PCR and immunochemical methods to investigate rCfex mRNA and protein expression and regulation by sex hormones in the pancreas, small intestine, liver, and kidneys from intact prepubertal and adult as well as gonadectomised adult rats treated with sex hormones. rCfex cDNA-transfected HEK293 cells were used to confirm the specificity of the commercial anti-CFEX antibody. Various biochemical parameters were measured in 24-h urine collected in metabolic cages. rCfex mRNA and related protein expression varied in all tested organs. Sex-independent expression of the rCfex protein was detected in pancreatic intercalated ducts (apical domain), small intestinal enterocytes (brush-border membrane; duodenum &gt; jejunum &gt; ileum), and hepatocytes (canalicular membrane). In kidneys, the rCfex protein was immunolocalised to the proximal tubule brush-border with segment-specific pattern (S1=S2&lt;S3), and both rCfex mRNA and protein expression exhibited male-dominant sex differences driven by stimulatory effects of androgens after puberty. However, urinary oxalate excretion was unrelated to renal rCfex protein expression. While the effect of male-dominant expression of rCfex in renal proximal tubules on urine oxalate excretion remains unknown, its expression in the hepatocyte canalicular membrane may be a pathway of oxalate elimination via bile.<\/jats:p>","DOI":"10.2478\/aiht-2018-69-3157","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T04:03:25Z","timestamp":1547179405000},"page":"286-303","source":"Crossref","is-referenced-by-count":7,"title":["Sex-independent expression of chloride\/formate exchanger Cfex (Slc26a6) in rat pancreas, small intestine, and liver, and male-dominant expression in kidneys"],"prefix":"10.2478","volume":"69","author":[{"given":"Dean","family":"Karaica","sequence":"first","affiliation":[{"name":"Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davorka","family":"Breljak","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jovica","family":"Lon\u010dar","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Ecotoxicology, Ru\u0111er Bo\u0161kovi\u0107 Institute, Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mila","family":"Lovri\u0107","sequence":"additional","affiliation":[{"name":"Clinical Institute of Laboratory Diagnosis, University Hospital Center, Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vedran","family":"Micek","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Vrhovac Maduni\u0107","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hrvoje","family":"Brzica","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol M.","family":"Herak-Kramberger","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana Ivkovi\u0107","family":"Dupor","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Ljubojevi\u0107","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tvrtko","family":"Smital","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Ecotoxicology, Ru\u0111er Bo\u0161kovi\u0107 Institute, Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u017deljka","family":"Vogrinc","sequence":"additional","affiliation":[{"name":"Clinical Institute of Laboratory Diagnosis, University Hospital Center, Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Burckhardt","sequence":"additional","affiliation":[{"name":"Institute for Systemic Physiology and Pathophysiology, University Medical Center G\u00f6ttingen, G\u00f6ttingen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitta C.","family":"Burckhardt","sequence":"additional","affiliation":[{"name":"Institute for Systemic Physiology and Pathophysiology, University Medical Center G\u00f6ttingen, G\u00f6ttingen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Saboli\u0107","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2019,1,11]]},"reference":[{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_001_w2aab3b7b3b1b6b1ab1ab1Aa","doi-asserted-by":"crossref","unstructured":"1. 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Effect of Slc26a6 deletion on apical Cl-\/HCO3- exchanger activity and cAMP-stimulated bicarbonate secretion in pancreatic duct. Am J Physiol-Gastr L 2007;292:G447-55. doi: 10.1152\/ajpgi.00286.2006","DOI":"10.1152\/ajpgi.00286.2006"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_007_w2aab3b7b3b1b6b1ab1ab7Aa","doi-asserted-by":"crossref","unstructured":"7. Simpson JE, Schweinfest CW, Shull GE, Gawenis LR, Walker NM, Boyle KT, Soleimani M, Clarke LL. PAT-1 (Slc26a6) is the predominant apical membrane Cl-\/HCO3- exchanger in the upper villous epithelium of the murine duodenum. Am J Physiol-Gastr L 2007;292:G1079-88. doi: 10.1152\/ajpgi.00354.2006","DOI":"10.1152\/ajpgi.00354.2006"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_008_w2aab3b7b3b1b6b1ab1ab8Aa","doi-asserted-by":"crossref","unstructured":"8. Stewart AK, Shmukler BE, Vandorpe DH, Reimold F, Heneghan JF, Nakakuki M, Akhavein A, Ko S, Ishiguro H, Alper SL. SLC26 anion exchangers of guinea pig pancreatic duct: molecular cloning and functional characterization. Am J Physiol-Cell Ph 2011;301:C289-303. doi: 10.1152\/ajpcell.00089.2011","DOI":"10.1152\/ajpcell.00089.2011"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_009_w2aab3b7b3b1b6b1ab1ab9Aa","doi-asserted-by":"crossref","unstructured":"9. Stewart AK, Yamamoto A, Nakakuki M, Kondo T, Alper SL, Ishiguro H. Functional coupling of apical Cl-\/HCO3- exchange with CFTR in stimulated HCO3- secretion by guinea pig interlobular pancreatic duct. Am J Physiol-Gastr L 2009;296:G1307-17. doi: 10.1152\/ajpgi.90697.2008","DOI":"10.1152\/ajpgi.90697.2008"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_010_w2aab3b7b3b1b6b1ab1ac10Aa","unstructured":"10. Petrovi\u0107 S, Ma L, Wang Z, Soleimani M. Identification of an apical Cl-\/HCO3- exchanger in rat kidney proximal tubule. Am J Physiol-Cell Ph 2003;285:C608-17. doi: 0.1152\/ajpcell.00084.2003"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_011_w2aab3b7b3b1b6b1ab1ac11Aa","doi-asserted-by":"crossref","unstructured":"11. Thomson RB, Wang T, Thomson BR, Tarrats L, Girardi A, Mentone S, Soleimani M, Kocher O, Aronson PS. Role of PDZK1 in membrane expression of renal brush border ion exchangers. P Natl Acad Sci USA 2005;102:13331-6. doi: 10.1073\/pnas.0506578102","DOI":"10.1073\/pnas.0506578102"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_012_w2aab3b7b3b1b6b1ab1ac12Aa","doi-asserted-by":"crossref","unstructured":"12. Kujala M, Tienari J, Lohi H, Elomaa O, Sariola H, Lehtonen E, Kere J. SLC26A6 and SLC26A7 anion exchangers have a distinct distribution in human kidney. Nephron Exp Nephrol 2005;101:e50-8. doi: 10.1159\/000086345","DOI":"10.1159\/000086345"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_013_w2aab3b7b3b1b6b1ab1ac13Aa","doi-asserted-by":"crossref","unstructured":"13. Lohi H, Kujala M, Kerkel\u00e4 E, Saarialho-Kere U, Kestil\u00e4 M, Kere J. Mapping of five new putative anion transporter genes in human and characterization of SLC26A6, a candidate gene for pancreatic anion exchanger. Genomics 2000;70:102-12. doi: 10.1006\/geno.2000.6355","DOI":"10.1006\/geno.2000.6355"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_014_w2aab3b7b3b1b6b1ab1ac14Aa","doi-asserted-by":"crossref","unstructured":"14. Lohi H, Lamprecht G, Markovich D, Heil A, Kujala M, Seidler U, Kere J. Isoforms of SLC26A6 mediate anion transport and have functional PDZ interaction domains. Am J Physiol-Cell Ph 2003;284:C769-79. doi: 10.1152\/ajpcell.00270.2002","DOI":"10.1152\/ajpcell.00270.2002"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_015_w2aab3b7b3b1b6b1ab1ac15Aa","doi-asserted-by":"crossref","unstructured":"15. Waldegger S, Moschen I, Ramirez A, Smith RJ, Ayadi H, Lang F, Kubisch C. Cloning and characterization of SLC26A6, a novel member of the solute carrier 26 gene family. Genomics 2001;72:43-50. doi: 10.1006\/geno.2000.6445","DOI":"10.1006\/geno.2000.6445"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_016_w2aab3b7b3b1b6b1ab1ac16Aa","doi-asserted-by":"crossref","unstructured":"16. Knauf F, Yang CL, Thomson RB, Mentone SA, Giebisch G, Aronson PS. Identification of a chloride-formate exchanger expressed on the brush border membrane of renal proximal tubule cells. P Natl Acad Sci USA 2001;98:9425-30. doi: 10.1073\/pnas.141241098","DOI":"10.1073\/pnas.141241098"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_017_w2aab3b7b3b1b6b1ab1ac17Aa","doi-asserted-by":"crossref","unstructured":"17. Xie Q, Welch R, Mercado A, Romero MF, Mount DB, Michael F. Molecular characterization of the murine Slc26a6 anion exchanger: functional comparison with Slc26a1. Am J Physiol-Renal 2002;283:F826-38. doi: 10.1152\/ajprenal.00079.2002","DOI":"10.1152\/ajprenal.00079.2002"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_018_w2aab3b7b3b1b6b1ab1ac18Aa","doi-asserted-by":"crossref","unstructured":"18. Wang Z, Petrovi\u0107 S, Mann E, Soleimani M. Identification of an apical Cl-\/HCO3- exchanger in the small intestine. Am J Physiol-Gastr L 2002;282:G573-9. doi: 10.1152\/ajpgi.00338.2001","DOI":"10.1152\/ajpgi.00338.2001"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_019_w2aab3b7b3b1b6b1ab1ac19Aa","doi-asserted-by":"crossref","unstructured":"19. Gholami K, Muniandy S, Salleh N. Progesterone downregulates oestrogen-induced expression of CFTR and SLC26A6 proteins and mRNA in rats\u2019 uteri. J Biomed Biotechnol 2012;2012:596084. doi: 10.1155\/2012\/596084","DOI":"10.1155\/2012\/596084"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_020_w2aab3b7b3b1b6b1ab1ac20Aa","doi-asserted-by":"crossref","unstructured":"20. Garc\u00eda M, Hern\u00e1ndez-Lorenzo P, San Rom\u00e1n JI, Calvo JJ. Pancreatic duct secretion: experimental methods, ion transport mechanisms and regulation. J Physiol Biochem 2008;64:243-57. doi: 10.1007\/BF03178846","DOI":"10.1007\/BF03178846"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_021_w2aab3b7b3b1b6b1ab1ac21Aa","doi-asserted-by":"crossref","unstructured":"21. Saint-Criq V, Gray MA. Role of CFTR in epithelial physiology. Cell Mol Life Sci 2016;74:93-115. doi: 10.1007\/s00018-016-2391-y","DOI":"10.1007\/s00018-016-2391-y"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_022_w2aab3b7b3b1b6b1ab1ac22Aa","doi-asserted-by":"crossref","unstructured":"22. Petrovi\u0107 S, Wang Z, Ma L, Seidler U, Forte JG, Shull GE, Soleimani M. Colocalization of the apical Cl-\/HCO3- exchanger PAT1 and gastric H-K-ATPase in stomach parietal cells. Am J Physiol-Gastr L 2002;283:G1207-16. doi: 0.1152\/ajpgi.00137.2002","DOI":"10.1152\/ajpgi.00137.2002"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_023_w2aab3b7b3b1b6b1ab1ac23Aa","doi-asserted-by":"crossref","unstructured":"23. Alvarez BV, Kieller DM, Quon AL, Markovich D, Casey JR. Slc26a6: a cardiac chloride-hydroxyl exchanger and predominant chloride-bicarbonate exchanger of the mouse heart. J Physiol 2004;561:721-34. doi: 10.1113\/jphysiol.2004.077339","DOI":"10.1113\/jphysiol.2004.077339"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_024_w2aab3b7b3b1b6b1ab1ac24Aa","doi-asserted-by":"crossref","unstructured":"24. Kim HJ, Myers R, Sihn C-R, Rafizadeh S, Zhang X-D. Slc26a6 functions as an electrogenic Cl-\/HCO3- exchanger in cardiac myocytes. Cardiovasc Res 2013;100:383-91. doi: 10.1093\/cvr\/cvt195","DOI":"10.1093\/cvr\/cvt195"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_025_w2aab3b7b3b1b6b1ab1ac25Aa","doi-asserted-by":"crossref","unstructured":"25. 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Am J Physiol-Gastr L 2001;281:G1301-8. doi: 10.1152\/ajpgi.2001.281.5.G1301","DOI":"10.1152\/ajpgi.2001.281.5.G1301"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_028_w2aab3b7b3b1b6b1ab1ac28Aa","doi-asserted-by":"crossref","unstructured":"28. Knauf F, Ko N, Jiang Z, Robertson WG, Van Itallie CM, Anderson JM, Aronson PS. Net intestinal transport of oxalate reflects passive absorption and SLC26A6-mediated secretion. J Am Soc Nephrol 2011;22:2247-55. doi: 10.1681\/ASN.2011040433","DOI":"10.1681\/ASN.2011040433"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_029_w2aab3b7b3b1b6b1ab1ac29Aa","doi-asserted-by":"crossref","unstructured":"29. Wang Z, Wang T, Petrovi\u0107 S, Tuo B, Riederer B, Barone SL, Lorenz JN, Seidler U, Aronson PS, Soleimani M. Renal and intestinal transport defects in Slc26a6-null mice. Am J Physiol-Cell Ph 2005;288:C957-65. doi: 10.1152\/ajpcell.00505.2004","DOI":"10.1152\/ajpcell.00505.2004"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_030_w2aab3b7b3b1b6b1ab1ac30Aa","doi-asserted-by":"crossref","unstructured":"30. Thomson RB, Thomson CL, Aronson PS. N-glycosylation critically regulates function of oxalate transporter SLC26A6. Am J Physiol-Cell Ph 2016;311:C866-73. doi: 10.1152\/ajpcell.00171.2016","DOI":"10.1152\/ajpcell.00171.2016"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_031_w2aab3b7b3b1b6b1ab1ac31Aa","doi-asserted-by":"crossref","unstructured":"31. Hassan HA, Mentone S, Karniski LP, Rajendran VM, Aronson PS. Regulation of anion exchanger Slc26a6 by protein kinase C. Am J Physiol-Cell Ph 2007;292:C1485-92. doi: 10.1152\/ajpcell.00447.2006","DOI":"10.1152\/ajpcell.00447.2006"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_032_w2aab3b7b3b1b6b1ab1ac32Aa","doi-asserted-by":"crossref","unstructured":"32. Ohana E, Shcheynikov N, Moe OW, Muallem S. SLC26A6 and NaDC-1 transporters interact to regulate oxalate and citrate homeostasis. J Am Soc Nephrol 2013;24:1617-26. doi: 10.1681\/ASN.2013010080","DOI":"10.1681\/ASN.2013010080"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_033_w2aab3b7b3b1b6b1ab1ac33Aa","doi-asserted-by":"crossref","unstructured":"33. Dawson PA, Russell CS, Lee S, McLeay SC, van Dongen JM, Cowley DM, Clarke LA, Markovich D. Urolithiasis and hepatotoxicity are linked to the anion transporter Sat1 in mice. J Clin Invest 2010;120:706-12. doi: 10.1172\/JCI31474","DOI":"10.1172\/JCI31474"},{"key":"2026070104592830333_j_aiht-2018-69-3157_ref_034_w2aab3b7b3b1b6b1ab1ac34Aa","doi-asserted-by":"crossref","unstructured":"34. Jiang Z, Asplin JR, Evan AP, Rajendran VM, Velazquez H, Nottoli TP, Binder HJ, Aronson PS. Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6. 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