Ectopic expression of CLDN2 in podocytes is associated with childhood onset nephrotic syndrome

Abstract

Background: Animal models of nephrotic syndrome (NS) revealed that tight junction (TJ)-like structures are generated together with a concomitant decrease in slit diaphragms (SDs). Claudins (CLDNs) are capable of forming TJ strands and thereby the backbone of TJs. We showed the ectopic expression of CLDN2 in podocytes in pediatric NS, and detected its localization. Methods: Renal frozen specimens were obtained by biopsy from 49 pediatric patients: 21 subjects with MCD, 18 with FSGS, and 10 with IgA nephritis (IgA-N). CLDN2 expression was observed by immunohistochemistry and the CLDN2-positive area was calculated. Moreover, its localization was detected using immunoelectron microscopy. Results: CLDN2 is ectopically detected in cases with MCD and FSGS before remission. The CLDN2-stained region in MCD and FSGS glomeruli before remission was significantly greater than that after remission as well as in IgA-N patients. Immunoelectron microscopy revealed that CLDN2 was concentrated along newly formed TJs in podocytes. Conclusion: The same pathological findings in terms of ectopic CLDN2 expression in podocytes were shown in cases with MCD and FSGS before remission. Immunofluorescence and immunoelectron studies of CLDN2 appear to afford a powerful tool for the diagnosis of primary NS. In addition, CLDN2 expression level may be related to disease status.