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Montelukast improves the changes of cytoskeletal and adaptor proteins of human podocytes by interleukin-13

 Tae-Sun Ha  ;  Ja Ae Nam  ;  Su-Bin Seong  ;  Moin A. Saleem  ;  Se Jin Park  ;  Jae Il Shin 
 INFLAMMATION RESEARCH, Vol.66(9) : 793-802, 2017 
Journal Title
Issue Date
Acetates/pharmacology* ; Actinin/metabolism ; Adaptor Proteins, Signal Transducing/metabolism ; B7-1 Antigen/metabolism ; Cells, Cultured ; Crk-Associated Substrate Protein/metabolism ; Cytoskeletal Proteins/metabolism ; Humans ; Interleukin-13/pharmacology* ; Leukotriene Antagonists/pharmacology* ; Microfilament Proteins/metabolism ; Podocytes/drug effects* ; Podocytes/metabolism ; Podocytes/ultrastructure ; Quinolines/pharmacology* Zonula Occludens-1 Protein/metabolism ; beta Catenin/metabolism
B7-1 ; Cytoskeletal molecules ; Interleukin-13 ; Leukotriene receptor antagonists ; Podocytes ; Slit diaphragm
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.
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1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
Yonsei Authors
Shin, Jae Il(신재일) ORCID logo https://orcid.org/0000-0003-2326-1820
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