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

Research output: Contribution to journalArticle (Academic Journal)peer-review

2 Citations (Scopus)
239 Downloads (Pure)

Abstract

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.

Original languageEnglish
Pages (from-to)793-802
Number of pages10
JournalInflammation Research
Volume66
Issue number9
Early online date12 Jun 2017
DOIs
Publication statusPublished - Sep 2017

Keywords

  • Interleukin-13
  • Slit diaphragm
  • Cytoskeletal molecules
  • B7-1
  • Podocytes
  • Leukotriene receptor antagonists

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