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

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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
DOIs
Publication statusPublished - 2017 Sep 1

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montelukast
Plakins
Podocytes
Interleukin-13
Lipoid Nephrosis
Actinin
Tight Junctions
Diaphragm
Crk-Associated Substrate Protein
human interleukin-13
Cytokines
Catenins

All Science Journal Classification (ASJC) codes

  • Immunology
  • Pharmacology

Cite this

Ha, Tae Sun ; Nam, Ja Ae ; Seong, Su Bin ; Saleem, Moin A. ; Park, Se Jin ; Shin, Jae Il. / Montelukast improves the changes of cytoskeletal and adaptor proteins of human podocytes by interleukin-13. In: Inflammation Research. 2017 ; Vol. 66, No. 9. pp. 793-802.
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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.",
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Montelukast improves the changes of cytoskeletal and adaptor proteins of human podocytes by interleukin-13. / Ha, Tae Sun; Nam, Ja Ae; Seong, Su Bin; Saleem, Moin A.; Park, Se Jin; Shin, Jae Il.

In: Inflammation Research, Vol. 66, No. 9, 01.09.2017, p. 793-802.

Research output: Contribution to journalArticle

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AU - Nam, Ja Ae

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AU - Saleem, Moin A.

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AU - Shin, Jae Il

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AB - 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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