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

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.