Montelukast improves the changes of cytoskeletal and adaptor proteins of human podocytes by interleukin-13
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.
Human conditionally immortalized podocytes were used.
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.
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.
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.
KeywordsInterleukin-13 Slit diaphragm Cytoskeletal molecules B7-1 Podocytes Leukotriene receptor antagonists
The authors would like to thank Keum Hwa Lee for arranging references and proof reading.
T-SH, JAN, S-BS, MAS, SJP and JIS designed study, coordinated data acquisition, statistically analyzed and interpreted the data, drafted and revised the manuscript. All authors read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
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.