Logo Annals of Transplantation Logo Annals of Transplantation Logo Annals of Transplantation

25 November 2016 : Original article  

CXC Chemokine Receptor 4 (CXCR4) Antagonist, a Novel Pathway to Prevent Chronic Allograft Nephropathy

Yue XuABCDEF, Qiang ZhangBCD, Wenrui XueCDF, Song ZengDEF, Zijian ZhangBCD, Xiaodong ZhangEFG, Xiaopeng HuAEFG

DOI: 10.12659/AOT.899492

Ann Transplant 2016; 21:728-734

Abstract

BACKGROUND: Chronic allograft nephropathy (CAN) remains a major problem for long-term graft survival and different pathways participate in its development. CXC chemokine receptor 4 (CXCR4) is significantly upregulated following renal injury and fibrotic response. We investigated the effect of AMD3100, a CXCR4 antagonist, on the development of CAN in rat models.

MATERIAL AND METHODS: CAN rat models (n=20) were established using male Fisher 344 to Lewis rats. Rats in the experimental group (n=10) were treated with AMD3100 (1 mg/kg/day subcutaneously, 0–12 weeks), rats in the control group (n=10) were treated with saline. The serum creatinine levels were monitored every week. Kidney grafts were harvested 12 weeks after modeling for histological analysis. We used chronic allograft damage index (CADI) scores to evaluate each group. Q-PCR and Western blotting were used to measure CXCR4, TGF-β1/Smad3 signaling pathway and α-smooth muscle actin (α-SMA) expression in renal allograft tissue.

RESULTS: CXCR4 expression was increased significantly in the control group which developed intense chronic changes after 12 weeks. Histological changes of CAN in the experimental group were ameliorated by AMD3100 which also had better graft function compare to the control group. AMD3100 significantly blunted the increase in the mRNA expression level of CXCR4, TGF-β1/Smad3, and α-SMA. A significant reduction in TGF-β1 and α-SMA protein content was observed only in the experimental group as shown in a representative Western blot.

CONCLUSIONS: Based on these findings, CXCR4 expression may mediate in part the development of CAN. AMD3100 may ameliorate histological changes of CAN and maintain better allograft function. It blunts downstream effects of TGF-β1 signaling and fibroblast activation. Therefore, antagonism of CXCR4 may provide a novel way to prevent the development of CAN.

Keywords: Kidney Transplantation, Receptors, CXCR4, Transforming Growth Factor beta, Transplantation Tolerance

Comments

In Press

06 May 2022 : Original article  

Phosphatidylethanol (PEth) for Monitoring Sobriety in Liver Transplant Candidates: Preliminary Results of D...

Ann Transplant In Press; DOI: 10.12659/AOT.936293  

Most Viewed Current Articles

26 Jan 2022 : Review article  

Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Risk Factors and Predictive Models

DOI :10.12659/AOT.934924

Ann Transplant 2022; 27:e934924

29 Dec 2021 : Original article  

Efficacy and Safety of Tacrolimus-Based Maintenance Regimens in De Novo Kidney Transplant Recipients: A Sys...

DOI :10.12659/AOT.933588

Ann Transplant 2021; 26:e933588

24 Jul 2020 : Review article  

Kidney Transplantation in the Times of COVID-19 – A Literature Review

DOI :10.12659/AOT.925755

Ann Transplant 2020; 25:e925755

15 Mar 2022 : Case report  

Combined Liver, Pancreas-Duodenum, and Kidney Transplantation for Patients with Hepatitis B Cirrhosis, Urem...

DOI :10.12659/AOT.935860

Ann Transplant 2022; 27:e935860

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358