Objective and design: Interleukin-13 (IL-13) has recently been reported to be a potential cytokine in the pathogenesis of minimal-change nephrotic syndrome (MCNS). However, the mechanistic insights associated with podocyte dysfunction mediated by IL-13-induced changes in various slit diaphragm (SD) and cytoskeletal molecules have not yet been shown in cultured human podocytes in vitro. Materials: Human conditionally immortalized podocytes were used. Treatment: Podocytes were incubated with various concentrations of IL-13 during the indicated time periods (6, 12, and 24 h) and montelukast was administered with the dose of 0.1 μg. Results: Treatment of IL-13 resulted in a progressive decrease in distinct processes or projections of the human podocytes and high dose of IL-13 increased podocyte permeability in vitro at 6 h. IL-13 had a substantial impact on the redistribution and rearrangement of zonula occludens (ZO)-1, synaptopodin, α-actinin, CD2-associated protein (CD2AP) in podocytes and disrupted the cytoskeletal connections in a concentration-dependent manner on confocal microscopy. IL-13 also down-modulated ZO-1, synaptopodin, α-actinin, CD2AP, and p130Cas at protein levels and upregulated β-catenin and B7-1 in podocytes. Furthermore, we demonstrated that down-modulated changes in various SD and cytoskeletal structures of human podocytes induced by IL-13 was significantly restored after treatment with montelukast with upregulation of B7-1. Conclusion: Our results suggest that targeting IL-13 may be one of the important cytokines in the pathogenesis of MCNS and targeting IL-13 could be one of the potential therapeutic strategies in MCNS.
Bibliographical noteFunding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) and funded by the Ministry of Education, Science and Technology (2011-0013789, 2013R1A1A1012112 and 2015R1C1A1A01052984) to J.I. Shin and partly supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2013R1A1A4A03006207) to T.-S. Ha.
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