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Mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-LDL and its receptor, LOX-1

  • Authors:
    • Shi Deng
    • Tao Jin
    • Li Zhang
    • Hong Bu
    • Peng Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
    Copyright: © Deng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4124-4134
    |
    Published online on: September 13, 2016
       https://doi.org/10.3892/mmr.2016.5735
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Abstract

Chronic renal allograft dysfunction (CRAD) is the most common cause of graft failure following renal transplantation. However, the underlying mechanisms remain to be fully elucidated. Immunosuppressants and hyperlipidemia are associated with renal fibrosis following long‑term use. The present study aimed to determine the effects of tacrolimus (FK506) and lipid metabolism disorder on CRAD. In vitro and in vivo models were used for this investigation. Cells of the mouse proximal renal tubular epithelial cell strain, NRK‑52E, were cultured either with oxidized low‑density lipoprotein (ox‑LDL), FK506, ox‑LDL combined with FK506, or vehicle, respectively. Changes in cell morphology and changes in the levels of lectin‑like ox‑LDL receptor‑1 (LOX‑1), reactive oxygen species (ROS), hydrogen peroxide and fibrosis‑associated genes were evaluated at 24, 48 and 72 h. In separate experiment, total of 60 Sprague‑Dawley rats were divided randomly into four groups, which included a high‑fat group, FK506 group, high‑fat combined with FK506 group, and control group. After 2, 4 and 8 weeks, the serum lipid levels, the levels of ox‑LDL, ROS, and the expression levels of transforming growth factor (TGF)‑β1 and connective tissue growth factor were determined. The in vitro and in vivo models revealed that lipid metabolism disorder and FK506 caused oxidative stress and a fibrogenic response. In addition, decreased levels of LOX‑1 markedly reduced the levels of TGF‑β1 in the in vitro model. Taken together, FK506 and dyslipidemia were found to be associated with CRAD following transplantation.
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Copy and paste a formatted citation
Spandidos Publications style
Deng S, Jin T, Zhang L, Bu H and Zhang P: Mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-LDL and its receptor, LOX-1. Mol Med Rep 14: 4124-4134, 2016.
APA
Deng, S., Jin, T., Zhang, L., Bu, H., & Zhang, P. (2016). Mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-LDL and its receptor, LOX-1. Molecular Medicine Reports, 14, 4124-4134. https://doi.org/10.3892/mmr.2016.5735
MLA
Deng, S., Jin, T., Zhang, L., Bu, H., Zhang, P."Mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-LDL and its receptor, LOX-1". Molecular Medicine Reports 14.5 (2016): 4124-4134.
Chicago
Deng, S., Jin, T., Zhang, L., Bu, H., Zhang, P."Mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-LDL and its receptor, LOX-1". Molecular Medicine Reports 14, no. 5 (2016): 4124-4134. https://doi.org/10.3892/mmr.2016.5735
Copy and paste a formatted citation
x
Spandidos Publications style
Deng S, Jin T, Zhang L, Bu H and Zhang P: Mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-LDL and its receptor, LOX-1. Mol Med Rep 14: 4124-4134, 2016.
APA
Deng, S., Jin, T., Zhang, L., Bu, H., & Zhang, P. (2016). Mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-LDL and its receptor, LOX-1. Molecular Medicine Reports, 14, 4124-4134. https://doi.org/10.3892/mmr.2016.5735
MLA
Deng, S., Jin, T., Zhang, L., Bu, H., Zhang, P."Mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-LDL and its receptor, LOX-1". Molecular Medicine Reports 14.5 (2016): 4124-4134.
Chicago
Deng, S., Jin, T., Zhang, L., Bu, H., Zhang, P."Mechanism of tacrolimus-induced chronic renal fibrosis following transplantation is regulated by ox-LDL and its receptor, LOX-1". Molecular Medicine Reports 14, no. 5 (2016): 4124-4134. https://doi.org/10.3892/mmr.2016.5735
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