Interleukin-13 may increase podocyte permeability via modulation of zonula occludens-1
Other Titles
Zonula occludens-1의 변화를 통한 interleukin-13의 족세포 투과도 증가
Authors
박세진
Department
Dept. of Pediatrics (소아청소년과학교실)
Issue Date
2013
Description
Dept. of Medicine/박사
Abstract
Purpose: The aim of this study was to investigate whether pathologic changes in zonula occludens-1 (ZO-1) are induced by interleukin-13 (IL-13) in the experimental minimal-change nephrotic syndrome (MCNS) model and to determine whether montelukast, a leukotriene receptor antagonist, has an effect on ZO-1 production in cultured human podocytes.Materials and methods: Human podocytes cultured on bovine serum albumin-coated plates were treated with different doses of IL-13 and montelukast and examined for permeability using monolayer semi-permeable membranes, for distribution using confocal microscopy, and for ZO-1 protein levels using Western blotting. Results: At higher doses, IL-13 gradually increased the permeability of monolayered podocytes. The redistribution and rearrangement of ZO-1 by IL-13 was observed in immunofluorescence studies. ZO-1 was internalized and shown to accumulate in the cytoplasm of human podocytes in an IL-13 dose-dependent manner. High doses (50 and 100 ng/mL) of IL-13 decreased the levels of ZO-1 protein at 12 and 24 hr (both P < 0.01; n=3), which were significantly reversed by a high dose (0.5 μM) montelukast treatment (P < 0.01, n=3).Conclusions: Our results suggest that IL-13 may increase podocyte permeability through the modulation of ZO-1, and such alterations in the content and localization of ZO-1 may be relevant to the pathogenesis of proteinuria in the IL-13-induced MCNS model. In addition, the leukotriene receptor antagonist montelukast may be a potential therapeutic option for the treatment of IL-13-induced MCNS.