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Tacrolimus increases the expression level of the chemokine receptor CXCR2 to promote renal fibrosis progression

Tacrolimus is one of the most used and effective immunosuppressive agents currently available in the clinic; however, its use is limited by nephrotoxicity, which is the main secondary effect of this drug. The mechanisms underlying tacrolimus-induced nephrotoxicity remain unknown. The present study a...

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Autores principales: Wang, Dongdong, Chen, Xiao, Fu, Meng, Xu, Hong, Li, Zhiping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844638/
https://www.ncbi.nlm.nih.gov/pubmed/31638188
http://dx.doi.org/10.3892/ijmm.2019.4368
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author Wang, Dongdong
Chen, Xiao
Fu, Meng
Xu, Hong
Li, Zhiping
author_facet Wang, Dongdong
Chen, Xiao
Fu, Meng
Xu, Hong
Li, Zhiping
author_sort Wang, Dongdong
collection PubMed
description Tacrolimus is one of the most used and effective immunosuppressive agents currently available in the clinic; however, its use is limited by nephrotoxicity, which is the main secondary effect of this drug. The mechanisms underlying tacrolimus-induced nephrotoxicity remain unknown. The present study aimed to investigate the mechanism underlying tacrolimus-induced nephrotoxicity and to identify novel potential targets. Masson staining, Sirius red staining and periodic acid-silver methenamine staining were used to observe kidney pathological changes. Immunohistochemical and immunofluorescent analyses were performed to examine the expression levels of vimentin, E-cadherin and α-smooth muscle actin (α-SMA). Transcriptomics and bioinformatics analyses were performed to investigate the nephrotoxicity mechanism induced by tacrolimus using RNA-sequencing, differentially expressed genes identification and annotation, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. The present results demonstrated that compared with the normal control group, the tacrolimus nephrotoxicity group exhibited severe renal fibrosis (P<0.05), upregulated vimentin (P<0.01), downregulated E-cadherin (P<0.05) and upregulated α-SMA (P<0.01). Transcriptomics and bioinformatics analyses identified the pathway 'cytokine-cytokine receptor interaction' as the most significantly enriched (P<0.05). Moreover, KEGG pathway enrichment analysis identified that tacrolimus increased the expression levels of chemokine (C-X-C) motif ligand (CXCL)1, CXCL2 and CXCL3 and the chemokine receptor C-X-C chemokine receptor type 2 (CXCR2). Collectively, the present study suggested that tacrolimus increases the level of chemokine receptor CXCR2 to promote renal fibrosis progression, which is one of the potential mechanisms underlying tacrolimus-induced nephrotoxicity.
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spelling pubmed-68446382019-11-13 Tacrolimus increases the expression level of the chemokine receptor CXCR2 to promote renal fibrosis progression Wang, Dongdong Chen, Xiao Fu, Meng Xu, Hong Li, Zhiping Int J Mol Med Articles Tacrolimus is one of the most used and effective immunosuppressive agents currently available in the clinic; however, its use is limited by nephrotoxicity, which is the main secondary effect of this drug. The mechanisms underlying tacrolimus-induced nephrotoxicity remain unknown. The present study aimed to investigate the mechanism underlying tacrolimus-induced nephrotoxicity and to identify novel potential targets. Masson staining, Sirius red staining and periodic acid-silver methenamine staining were used to observe kidney pathological changes. Immunohistochemical and immunofluorescent analyses were performed to examine the expression levels of vimentin, E-cadherin and α-smooth muscle actin (α-SMA). Transcriptomics and bioinformatics analyses were performed to investigate the nephrotoxicity mechanism induced by tacrolimus using RNA-sequencing, differentially expressed genes identification and annotation, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. The present results demonstrated that compared with the normal control group, the tacrolimus nephrotoxicity group exhibited severe renal fibrosis (P<0.05), upregulated vimentin (P<0.01), downregulated E-cadherin (P<0.05) and upregulated α-SMA (P<0.01). Transcriptomics and bioinformatics analyses identified the pathway 'cytokine-cytokine receptor interaction' as the most significantly enriched (P<0.05). Moreover, KEGG pathway enrichment analysis identified that tacrolimus increased the expression levels of chemokine (C-X-C) motif ligand (CXCL)1, CXCL2 and CXCL3 and the chemokine receptor C-X-C chemokine receptor type 2 (CXCR2). Collectively, the present study suggested that tacrolimus increases the level of chemokine receptor CXCR2 to promote renal fibrosis progression, which is one of the potential mechanisms underlying tacrolimus-induced nephrotoxicity. D.A. Spandidos 2019-12 2019-10-10 /pmc/articles/PMC6844638/ /pubmed/31638188 http://dx.doi.org/10.3892/ijmm.2019.4368 Text en Copyright: © Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Wang, Dongdong
Chen, Xiao
Fu, Meng
Xu, Hong
Li, Zhiping
Tacrolimus increases the expression level of the chemokine receptor CXCR2 to promote renal fibrosis progression
title Tacrolimus increases the expression level of the chemokine receptor CXCR2 to promote renal fibrosis progression
title_full Tacrolimus increases the expression level of the chemokine receptor CXCR2 to promote renal fibrosis progression
title_fullStr Tacrolimus increases the expression level of the chemokine receptor CXCR2 to promote renal fibrosis progression
title_full_unstemmed Tacrolimus increases the expression level of the chemokine receptor CXCR2 to promote renal fibrosis progression
title_short Tacrolimus increases the expression level of the chemokine receptor CXCR2 to promote renal fibrosis progression
title_sort tacrolimus increases the expression level of the chemokine receptor cxcr2 to promote renal fibrosis progression
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844638/
https://www.ncbi.nlm.nih.gov/pubmed/31638188
http://dx.doi.org/10.3892/ijmm.2019.4368
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