Expression and subcellular localization of NHE₃ in the human gallbladder epithelium

Enhanced gallbladder concentrating function is an important factor for the pathogenesis of cholesterol gallstone disease (CGD), but the mechanism is unknown. Potential candidates for regulation of gallbladder ion absorption are suggested to be Na(+)/H(+) exchanger isoform 3 (NHE3). In this study, we investigated the expression and subcellular localization of NHE3 in both acalculous and calculous human gallbladders.

Adult human gallbladder tissue was obtained from 23 patients (7 men, 16 women) who had undergone cholecystectomy. The patients were divided into two groups: Group A (acalculous group) and Group B (calculous group). Gene expression of NHE3 was quantitatively estimated by real-time PCR. Protein expression was studied by Western blotting assays. Furthermore, expression of immunoreactive NHE3 was investigated by immunohistochemistry.

There was no significant difference in the NHE3 mRNA expression between calculous and acalculous human gallbladders. NHE3 protein expression in gallbladders from patients with cholelithiasis is increased compared to those without gallstones. Immunohistochemistry studies prove that NHE3 is located both on the apical plasma membrane and in the intracellular pool in human GBECs.

NHE3 may play a role in the pathogenesis of human CGD. Additional studies are required to further delineate the underlying mechanisms.