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Article Open Access

SDF‑1/CXCR4 induces epithelial‑mesenchymal transition through activation of the Wnt/β‑catenin signaling pathway in rat chronic allograft nephropathy

  • Authors:
    • Hao Tang
    • Yue Xu
    • Zijian Zhang
    • Song Zeng
    • Wenbo Dong
    • Wenjiao Jiao
    • Xiaopeng Hu
  • View Affiliations / Copyright

    Affiliations: Urology Institute of Capital Medical University, Department of Urology, Capital Medical University Beijing Chaoyang Hospital, Beijing 100020, P.R. China
    Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3696-3706
    |
    Published online on: March 15, 2019
       https://doi.org/10.3892/mmr.2019.10045
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Abstract

Epithelial‑mesenchymal transition (EMT) has been demonstrated to serve a crucial role in the progression of interstitial fibrosis, which is one of the principal pathological features of chronic allograft nephropathy (CAN). However, to the best of our knowledge, the mechanisms of EMT in CAN have not been investigated. In the present study, the effect of stromal cell‑derived factor 1 (SDF‑1) and the Wnt signaling pathway on the progression of EMT following kidney transplantation was investigated. The CAN model was established using Fisher 344 and Lewis rats, treated with low‑dose cyclosporine with or without AMD3100. CAN was confirmed by the pathological alterations and chronic allograft damage index scoring, and EMT was confirmed by western blotting and reverse transcription‑quantitative polymerase chain reaction. In the AMD3100 group, there were lower expression levels of α‑SMA and higher expression levels of E‑cadherin, which indicated that CAN and EMT were ameliorated by AMD3100. The kidney tissue was analyzed using an mRNA + long noncoding (lnc)RNA microarray. A total of 506 mRNAs and 404 lncRNAs were demonstrated to be significantly differentially expressed between the two groups, which revealed the involvement of SDF‑1/CXC chemokine receptor 4 (CXCR4) and the Wnt pathway. SDF‑1 was demonstrated to induce EMT in vitro through the upregulation of α‑SMA, downregulation of E‑cadherin and the wound healing assay, and in the rat renal tubular epithelial cells via the nuclear accumulation of β‑catenin, which were all inhibited by either AMD3100 or DKK‑1. CXXC finger protein 5 (CXXC5), a negative regulator of the Wnt pathway, was downregulated following treatment with SDF‑1, which was inhibited by AMD3100 but not by DKK‑1. Thus, CXXC5 may be a regulator downstream of SDF‑1/CXCR4 in EMT. In conclusion, SDF‑1/CXCR4 induces EMT of renal tubular epithelial cells with the involvement of the Wnt pathway, which may be a novel mechanism and therapeutic target in kidney allograft fibrosis of rats.
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Copy and paste a formatted citation
Spandidos Publications style
Tang H, Xu Y, Zhang Z, Zeng S, Dong W, Jiao W and Hu X: SDF‑1/CXCR4 induces epithelial‑mesenchymal transition through activation of the Wnt/β‑catenin signaling pathway in rat chronic allograft nephropathy. Mol Med Rep 19: 3696-3706, 2019.
APA
Tang, H., Xu, Y., Zhang, Z., Zeng, S., Dong, W., Jiao, W., & Hu, X. (2019). SDF‑1/CXCR4 induces epithelial‑mesenchymal transition through activation of the Wnt/β‑catenin signaling pathway in rat chronic allograft nephropathy. Molecular Medicine Reports, 19, 3696-3706. https://doi.org/10.3892/mmr.2019.10045
MLA
Tang, H., Xu, Y., Zhang, Z., Zeng, S., Dong, W., Jiao, W., Hu, X."SDF‑1/CXCR4 induces epithelial‑mesenchymal transition through activation of the Wnt/β‑catenin signaling pathway in rat chronic allograft nephropathy". Molecular Medicine Reports 19.5 (2019): 3696-3706.
Chicago
Tang, H., Xu, Y., Zhang, Z., Zeng, S., Dong, W., Jiao, W., Hu, X."SDF‑1/CXCR4 induces epithelial‑mesenchymal transition through activation of the Wnt/β‑catenin signaling pathway in rat chronic allograft nephropathy". Molecular Medicine Reports 19, no. 5 (2019): 3696-3706. https://doi.org/10.3892/mmr.2019.10045
Copy and paste a formatted citation
x
Spandidos Publications style
Tang H, Xu Y, Zhang Z, Zeng S, Dong W, Jiao W and Hu X: SDF‑1/CXCR4 induces epithelial‑mesenchymal transition through activation of the Wnt/β‑catenin signaling pathway in rat chronic allograft nephropathy. Mol Med Rep 19: 3696-3706, 2019.
APA
Tang, H., Xu, Y., Zhang, Z., Zeng, S., Dong, W., Jiao, W., & Hu, X. (2019). SDF‑1/CXCR4 induces epithelial‑mesenchymal transition through activation of the Wnt/β‑catenin signaling pathway in rat chronic allograft nephropathy. Molecular Medicine Reports, 19, 3696-3706. https://doi.org/10.3892/mmr.2019.10045
MLA
Tang, H., Xu, Y., Zhang, Z., Zeng, S., Dong, W., Jiao, W., Hu, X."SDF‑1/CXCR4 induces epithelial‑mesenchymal transition through activation of the Wnt/β‑catenin signaling pathway in rat chronic allograft nephropathy". Molecular Medicine Reports 19.5 (2019): 3696-3706.
Chicago
Tang, H., Xu, Y., Zhang, Z., Zeng, S., Dong, W., Jiao, W., Hu, X."SDF‑1/CXCR4 induces epithelial‑mesenchymal transition through activation of the Wnt/β‑catenin signaling pathway in rat chronic allograft nephropathy". Molecular Medicine Reports 19, no. 5 (2019): 3696-3706. https://doi.org/10.3892/mmr.2019.10045
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