CFEX (Slc26a6) in rat kidneys, liver, and small intestine in an experimental model of oxalate nephrolitiasis

CFEX (chloride/formate exchanger ; Slc26a6) is an important anion exchanger of chloride, bicarbonate, oxalate (OX), formate, and hydroxyl ions in kidneys, liver, and the small intestine. Studies on CFEX-knockout mice indicated a possible role of CFEX in the development of hyperoxaluria and OX urolithiasis/nephrolithiasis, which in humans is more frequent in men. Here we studied the expression of the CFEX protein and mRNA in the organs of male and female rats, and employed a rat model of ethylene glycol (EG)-induced OX urolithiasis in order to correlate the expression of CFEX with sex-related hyperoxaluria. Rats drank EG in water (0.75 % vol/vol) or water (control) for 30 days. Tissue expressions of the CFEX protein and mRNA were analysed by immunochemical methods and qRT-PCR, respectively. The specificity of an anti-CFEX antibody, used in immunochemical studies, was confirmed in HEK293 cells transiently transfected with CFEX cDNA. In kidneys, the CFEX protein was immunolocalized to the proximal tubule brush-border membrane (BBM) with segmental (S3>>S1~S2) and sex (male>female) differences. Sex-unrelated expression was detected in the BBM of enterocytes (duodenum>jejunum) and in the hepatocyte canalicular membrane. In immunoblots, the CFEX protein band of ~120 kDa in various organs showed an expression pattern comparable to that in immunocytochemistry ; however, renal CFEX mRNA expression was not sex-dependent. Compared to controls and EG-treated females, the EG-treated male rats exhibited hyperoxalemia, hyperoxaluria and OX crystaluria, but the expression of CFEX mRNA and protein remained unaffected in the organs of both sexes. Thus, basic CFEX expression in both rat sexes was sufficient for OX handling even upon EG-treatment, indicating that in rats, CFEX plays no major role in generating EG-induced hyperoxaluria and nephrolithiasis.