Open Access

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

  • Authors:
    • Dongdong Wang
    • Xiao Chen
    • Meng Fu
    • Hong Xu
    • Zhiping Li
  • View Affiliations

  • Published online on: October 10, 2019     https://doi.org/10.3892/ijmm.2019.4368
  • Pages: 2181-2188
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

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.
View Figures
View References

Related Articles

Journal Cover

December-2019
Volume 44 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Wang D, Chen X, Fu M, Xu H and Li Z: Tacrolimus increases the expression level of the chemokine receptor CXCR2 to promote renal fibrosis progression. Int J Mol Med 44: 2181-2188, 2019.
APA
Wang, D., Chen, X., Fu, M., Xu, H., & Li, Z. (2019). Tacrolimus increases the expression level of the chemokine receptor CXCR2 to promote renal fibrosis progression. International Journal of Molecular Medicine, 44, 2181-2188. https://doi.org/10.3892/ijmm.2019.4368
MLA
Wang, D., Chen, X., Fu, M., Xu, H., Li, Z."Tacrolimus increases the expression level of the chemokine receptor CXCR2 to promote renal fibrosis progression". International Journal of Molecular Medicine 44.6 (2019): 2181-2188.
Chicago
Wang, D., Chen, X., Fu, M., Xu, H., Li, Z."Tacrolimus increases the expression level of the chemokine receptor CXCR2 to promote renal fibrosis progression". International Journal of Molecular Medicine 44, no. 6 (2019): 2181-2188. https://doi.org/10.3892/ijmm.2019.4368