Open Access

Renoprotective effect of erythropoietin via modulation of the STAT6/MAPK/NF-κB pathway in ischemia/reperfusion injury after renal transplantation

  • Authors:
    • Jinhua Zhang
    • Daqiang Zhao
    • Ning Na
    • Heng Li
    • Bin Miao
    • Liangqing Hong
    • Zhengyu Huang
  • View Affiliations

  • Published online on: October 20, 2017     https://doi.org/10.3892/ijmm.2017.3204
  • Pages:25-32
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ischemia/reperfusion injury (IRI) commonly occurs in renal transplantation. Erythropoietin (EPO) exerts a protective effect in IRI. To investigate the underlying molecular mechanism, rat models of renal IRI were established and treated with EPO and/or lentivirus‑mediated EPO-siRNA, the signal transducer and activator of transcription 6 (STAT6) inhibitor AS1517499, the JNK inhibitor SP600125, the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580, and the nuclear factor (NF)-κB inhibitor lactacystin. Histological examination revealed that EPO protected the kidney from IRI, through decreasing the extent of tissue congestion and inflammatory cell infiltration; however, EPO siRNA did not exert the same protective effect. In addition, the EPO level was inversely associated with renal IRI. EPO downregulated the expression of interferon-γ, interleukin (IL)-4, creatinine and caspase-3, and upregulated the expression of IL-10, thymic stromal lymphopoietin, STAT6, p-JNK and p-p38, while the opposite effects were observed with the administration of EPO-siRNA and the specific respective inhibitors. Further results revealed that MAPK (p-JNK and p-p38) acted upstream of NF-κB, and that NF-κB signaling regulated the expression of caspase-1 and -3, which may be responsible for the cytotoxicity associated with IRI. Taken together, the results of the present study demonstrated that EPO exerted a protective effect in renal IRI via the STAT6/MAPK/NF-κB pathway. This protective effect of EPO may improve reperfusion tolerance in ischemic kidneys and benefit transplant recipients.

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January 2018
Volume 41 Issue 1

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

2016 Impact Factor: 2.341
Ranked #21/128 Medicine Research and Experimental
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APA
Zhang, J., Zhao, D., Na, N., Li, H., Miao, B., Hong, L., & Huang, Z. (2018). Renoprotective effect of erythropoietin via modulation of the STAT6/MAPK/NF-κB pathway in ischemia/reperfusion injury after renal transplantation. International Journal of Molecular Medicine, 41, 25-32. https://doi.org/10.3892/ijmm.2017.3204
MLA
Zhang, J., Zhao, D., Na, N., Li, H., Miao, B., Hong, L., Huang, Z."Renoprotective effect of erythropoietin via modulation of the STAT6/MAPK/NF-κB pathway in ischemia/reperfusion injury after renal transplantation". International Journal of Molecular Medicine 41.1 (2018): 25-32.
Chicago
Zhang, J., Zhao, D., Na, N., Li, H., Miao, B., Hong, L., Huang, Z."Renoprotective effect of erythropoietin via modulation of the STAT6/MAPK/NF-κB pathway in ischemia/reperfusion injury after renal transplantation". International Journal of Molecular Medicine 41, no. 1 (2018): 25-32. https://doi.org/10.3892/ijmm.2017.3204