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; Smıth, Lee

doi:10.1007/s00011-017-1058-y

Cited by 10 publications

(9 citation statements)

References 34 publications

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“…As most primary MCNS cases exhibit a high response rate to corticosteroids, its pathogenesis has been speculated to be immune-mediated, especially involving T cell-associated mechanisms [1,4]. Therefore, multiple studies have been conducted to explore the immunological basis of NS [5][6][7][8][9][10][11][12][13], and several studies specifically suggested T-helper 2 lymphocyte (Th2)dependency by demonstrating over-activity of type 2 helper T cells (Th2) and decreased Th1/Th2 ratios, thus highlighting Th2 predominance in NS [8,14,15]. Therefore, more studies have been performed with an aim to validate the role of Th2 cytokines such as interleukin (IL)-4, IL-5, and IL-13 in NS [16][17][18][19][20][21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Interleukin-4 and Dexamethasone on RNA-Seq-Based Transcriptomic Profiling of Human Podocytes: A Potential Role in Minimal Change Nephrotic Syndrome

Lee

et al. 2021

JCM

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Interleukin-4 (IL-4) expression is implicated in the pathogenesis of nephrotic syndrome (NS). This study aimed to investigate the changes in the transcriptomes of human podocytes induced by IL-4 treatment and to analyze whether these changes could be affected by simultaneous steroid treatment. Three groups of human podocytes were treated with control, IL-4, and IL-4 plus dexamethasone (DEX), respectively. We performed whole-transcriptome sequencing to identify differentially expressed genes (DEGs) between the groups. We investigated relevant biological pathways using Gene Ontology (GO) enrichment analyses. We also attempted to compare and validate the DEGs with the genes listed in PodNet, a literature-based database on mouse podocyte genes. A total of 176 genes were differentially expressed among the three groups. GO analyses showed that pathways related to cytoskeleton organization and cell signaling were significantly enriched. Among them, 24 genes were listed in PodNet, and 12 of them were previously reported to be associated with IL-4-induced changes in human podocytes. Of the 12 genes, the expression levels of BMP4, RARB, and PLCE1 were reversed when podocytes were simultaneously treated with DEX. In conclusion, this study explored changes in the transcriptome profiles of human podocytes treated with IL-4. Few genes were reported in previous studies and were previously validated in experiments with human podocytes. We speculate that IL-4 may exert pathogenic effects on the transcriptome of human podocytes, and a few genes may be involved in the pathogenesis.

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Section: Introductionmentioning

confidence: 99%

The Effect of Interleukin-4 and Dexamethasone on RNA-Seq-Based Transcriptomic Profiling of Human Podocytes: A Potential Role in Minimal Change Nephrotic Syndrome

Lee

et al. 2021

JCM

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“…In 2007, Lai et al suggested that IL13 overexpression could lead to podocyte injury with downregulation of proteins such as nephrin, podocin, and dystroglycan and a concur rent upregulation of B71 in MCNS induced rat 17) . After that, our previous studies reported that IL13 was involved in the changes of ZO1 proteins in podocytes which could www.chikd.org be a pathogenesis of MCNS 14,18) . Other recent studies have shown that increase in IL13 production was to cause fre quent relapse in SSNS 13,19) .…”

Section: Discussionmentioning

confidence: 98%

Interleukin-13 Increases Podocyte Apoptosis in Cultured Human Podocytes

Lee¹,

Oh²,

Seong³

et al. 2018

Child Kidney Dis

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Podocytes are important architectures that maintain the crucial roles of glomerular filtration barrier functions. Despite this structural importance, however, the mechanisms of the changes in podocytes that can be an important pathogenesis of minimal change nephrotic syndrome (MCNS) are not clear yet. The aim of this study was to investigate whether apoptosis is induced by interleukin (IL)-13 in cultured human podocytes. Methods: Human podocytes were treated with different IL-13 doses and apoptotic cells were analyzed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL assay) and fluorescence-activated cell sorting (FACS). Results: The IL-13 increased the number of TUNEL-positive cells in a dose-dependent manner at 6 and 18 hours (P<0.05 and P<0.05, respectively). The apop tosis rate was appeared to be increased slightly in the IL-13-stimulated podocytes (8.63 %, 13.02%, and 14.46%; 3, 10 and 30 ng/mL, respectively) than in the control cells (7.66%) at 12 hours by FACS assay. Conclusion: Our study revealed that IL-13 expression may increase podocyte apoptosis. Blocking the IL-13 signal pathway can potentially play an important role in regulating the apoptosis of podocytes.

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“…We recently found pathological molecular changes in podocyte proteins by IL-13. We previously reported that IL-13 increased podocyte permeability through the modulation of ZO-1 110) , modulated the changes of cytoskeletal and adaptor proteins 111) , and increased podocyte apoptosis 112) , resulting in proteinuria and podocyte injury. However, the supposed role of circulating IL-13 in proteinuria in MCD patients is questionable because the elevated serum IL-13 levels were not found in MCD patients during relapse 66) and have been reported in patients with NS during remission compared with the controls 113) .…”

Section: Interleukin-13 (Il-13)mentioning

confidence: 99%

Circulating Permeability Factors in Idiopathic Nephrotic Syndrome

2019

Child Kidney Dis

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Nephrotic syndrome (NS) is a common chronic glomerular disease in children characterized by significant proteinuria with resulting hypoalbuminemia, edema, and hyperlipidemia. Renal biopsy findings of diffuse foot processes effacement on electron microscopy and minimal change disease, focal segmental glomerulosclerosis (FSGS), or diffuse mesangial proliferation on light microscopy. It has been speculated that circulating permeability factors would be implicated in the pathogenesis of NS because they have been reportedly detected in the sera of patients and in experimental models of induced proteinuria. Moreover, a substantial portion of the patients with primary FSGS recurrence shortly after trans plantation. This report reviews the current knowledge regarding the role of circu lating permeability factors in the pathogenesis of proteinuria in NS and suggests future targeted therapeutic approaches for NS.

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

Abstract: 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.

Cited by 10 publications

References 34 publications

The Effect of Interleukin-4 and Dexamethasone on RNA-Seq-Based Transcriptomic Profiling of Human Podocytes: A Potential Role in Minimal Change Nephrotic Syndrome

The Effect of Interleukin-4 and Dexamethasone on RNA-Seq-Based Transcriptomic Profiling of Human Podocytes: A Potential Role in Minimal Change Nephrotic Syndrome

Interleukin-13 Increases Podocyte Apoptosis in Cultured Human Podocytes

Circulating Permeability Factors in Idiopathic Nephrotic Syndrome

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