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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 / Copyright

    Affiliations: Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 25-32
    |
    Published online on: October 20, 2017
       https://doi.org/10.3892/ijmm.2017.3204
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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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1 

Naylor KL, Zou G, Leslie WD, Hodsman AB, Lam NN, McArthur E, Fraser LA, Knoll GA, Adachi JD, Kim SJ, et al: Risk factors for fracture in adult kidney transplant recipients. World J Transplant. 6:370–379. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, Held PJ and Port FK: Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 341:1725–1730. 1999. View Article : Google Scholar : PubMed/NCBI

3 

Kosieradzki M and Rowiński W: Ischemia/reperfusion injury in kidney transplantation: mechanisms and prevention. Transplant Proc. 40:3279–3288. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Hoshinaga K, Shiroki R, Fujita T, Kanno T and Naide Y: The fate of 359 renal allografts harvested from non-heart beating cadaver donors at a single center. Clin Transpl. 213–220. 1998.

5 

Perico N, Cattaneo D, Sayegh MH and Remuzzi G: Delayed graft function in kidney transplantation. Lancet. 364:1814–1827. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Gueler F, Gwinner W, Schwarz A and Haller H: Long-term effects of acute ischemia and reperfusion injury. Kidney Int. 66:523–527. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Bonventre JV and Yang L: Cellular pathophysiology of ischemic acute kidney injury. J Clin Invest. 121:4210–4221. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Devarajan P: Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol. 17:1503–1520. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Bajwa A, Kinsey GR and Okusa MD: Immune mechanisms and novel pharmacological therapies of acute kidney injury. Curr Drug Targets. 10:1196–1204. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Silver SA, Cardinal H, Colwell K, Burger D and Dickhout JG: Acute kidney injury: preclinical innovations, challenges, and opportunities for translation. Can J Kidney Health Dis. 2:302015. View Article : Google Scholar : PubMed/NCBI

11 

Liu QS, Cheng ZW, Xiong JG, Cheng S, He XF and Li XC: Erythropoietin pretreatment exerts anti-inflammatory effects in hepatic ischemia/reperfusion-injured rats via suppression of the TLR2/NF-κB pathway. Transplant Proc. 47:283–289. 2015. View Article : Google Scholar : PubMed/NCBI

12 

McCook O, Georgieff M, Scheuerle A, Möller P, Thiemermann C and Radermacher P: Erythropoietin in the critically ill: do we ask the right questions. Crit Care. 16:3192012. View Article : Google Scholar

13 

Akcay A, Nguyen Q and Edelstein CL: Mediators of inflammation in acute kidney injury. Mediators Inflamm. 137072:2009. View Article : Google Scholar

14 

Kono H, Nakagawa K, Morita S, Shinoda K, Mizuno R, Kikuchi E, Miyajima A, Umezawa K and Oya M: Effect of a novel nuclear factor-κB activation inhibitor on renal ischemia-reperfusion injury. Transplantation. 96:863–870. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Latanich CA and Toledo-Pereyra LH: Searching for NF-kappaB-based treatments of ischemia reperfusion injury. J Invest Surg. 22:301–315. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Bennett BL, Cruz R, Lacson RG and Manning AM: Interleukin-4 suppression of tumor necrosis factor alpha-stimulated E-selectin gene transcription is mediated by STAT6 antagonism of NF-kappaB. J Biol Chem. 272:10212–10219. 1997. View Article : Google Scholar : PubMed/NCBI

17 

Kato A, Yoshidome H, Edwards MJ and Lentsch AB: Reduced hepatic ischemia/reperfusion injury by IL-4: potential anti-inflammatory role of STAT6. Inflamm Res. 49:275–279. 2000. View Article : Google Scholar : PubMed/NCBI

18 

Yang Z, Zhong Z, Li M, Xiong Y, Wang Y, Peng G and Ye Q: Hypothermic machine perfusion increases A20 expression which protects renal cells against ischemia/reperfusion injury by suppressing inflammation, apoptosis and necroptosis. Int J Mol Med. 38:161–171. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Toronyi E: Role of apoptosis in the kidney after reperfusion. Orv Hetil. 149:305–315. 2008.In Hungarian. View Article : Google Scholar : PubMed/NCBI

20 

Hu H, Jiang W, Xi X, Zou C and Ye Z: MicroRNA-21 attenuates renal ischemia reperfusion injury via targeting caspase signaling in mice. Am J Nephrol. 40:215–223. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Haylor JL, Harris KP, Nicholson ML, Waller HL, Huang Q and Yang B: Atorvastatin improving renal ischemia reperfusion injury via direct inhibition of active caspase-3 in rats. Exp Biol Med (Maywood). 236:755–763. 2011. View Article : Google Scholar

22 

Fisher JW: Erythropoietin: physiology and pharmacology update. Exp Biol Med (Maywood). 228:1–14. 2003. View Article : Google Scholar

23 

Pellegrini L, Bennis Y, Velly L, Grandvuillemin I, Pisano P, Bruder N and Guillet B: Erythropoietin protects newborn rat against sevoflurane-induced neurotoxicity. Paediatr Anaesth. 24:749–759. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Liu L, Liu C, Hou L, Lv J, Wu F, Yang X, Ren S, Ji W, Wang M and Chen L: Protection against ischemia/reperfusion-induced renal injury by co treatment with erythropoietin and sodium selenite. Mol Med Rep. 12:7933–7940. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Zhang J, Zou YR, Zhong X, Deng HD, Pu L, Peng K and Wang L: Erythropoietin pretreatment ameliorates renal ischaemia-reperfusion injury by activating I3K/Akt signalling. Nephrology (Carlton). 20:266–272. 2015. View Article : Google Scholar

26 

Kwon MS, Kim MH, Kim SH, Park KD, Yoo SH, Oh IU, Pak S and Seo YJ: Erythropoietin exerts cell protective effect by activating I3K/Akt and MAPK pathways in C6 cells. Neurol Res. 36:215–223. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Li XJ, Zhang GX, Sun N, Sun Y, Yang LZ and Du YJ: Protective effects of erythropoietin on endotoxin-related organ injury in rats. J Huazhong Univ Sci Technolog Med Sci. 33:680–686. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Cugini D, Azzollini N, Gagliardini E, Cassis P, Bertini R, Colotta F, Noris M, Remuzzi G and Benigni A: Inhibition of the chemokine receptor CXCR2 prevents kidney graft function deterioration due to ischemia/reperfusion. Kidney Int. 67:1753–1761. 2005. View Article : Google Scholar : PubMed/NCBI

29 

Zeng Y, Adamson RH, Curry FR and Tarbell JM: Sphin-gosine-1-phosphate protects endothelial glycocalyx by inhibiting syndecan-1 shedding. Am J Physiol Heart Circ Physiol. 306:H363–H372. 2014. View Article : Google Scholar

30 

Zeng Y, Liu XH, Tarbell J and Fu B: Sphingosine 1-phosphate induced synthesis of glycocalyx on endothelial cells. Exp Cell Res. 339:90–95. 2015. View Article : Google Scholar : PubMed/NCBI

31 

Ratilal BO, Arroja MM, Rocha JP, Fernandes AM, Barateiro AP, Brites DM, Pinto RM, Sepodes BM and Mota-Filipe HD: Neuroprotective effects of erythropoietin pretreatment in a rodent model of transient middle cerebral artery occlusion. J Neurosurg. 121:55–62. 2014. View Article : Google Scholar : PubMed/NCBI

32 

Jun JH, Jun NH, Shim JK, Shin EJ and Kwak YL: Erythropoietin protects myocardium against ischemia-reperfusion injury under moderate hyperglycemia. Eur J Pharmacol. 745:1–9. 2014. View Article : Google Scholar : PubMed/NCBI

33 

Lu MJ, Chen YS, Huang HS and Ma MC: Erythropoietin alleviates post-ischemic injury of rat hearts by attenuating nitrosative stress. Life Sci. 90:776–784. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Xu X, Cao Z, Cao B, Li J, Guo L, Que L, Ha T, Chen Q, Li C and Li Y: Carbamylated erythropoietin protects the myocardium from acute ischemia/reperfusion injury through a I3K/Akt-dependent mechanism. Surgery. 146:506–514. 2009. View Article : Google Scholar : PubMed/NCBI

35 

Soranno DE, Rodell CB, Altmann C, Duplantis J, Andres-Hernando A, Burdick JA and Faubel S: Delivery of interleukin-10 via injectable hydrogels improves renal outcomes and reduces systemic inflammation following ischemic acute kidney injury in mice. Am J Physiol Renal Physiol. 311:F362–F372. 2016. View Article : Google Scholar : PubMed/NCBI

36 

Sun P, Liu J, Li W, Xu X, Gu X, Li H, Han H, Du C and Wang H: Human endometrial regenerative cells attenuate renal ischemia reperfusion injury in mice. J Transl Med. 14:282016. View Article : Google Scholar : PubMed/NCBI

37 

Segawa R, Mizuno N, Hatayama T, Jiangxu D, Hiratsuka M, Endo Y and Hirasawa N: Lipopolysaccharide-activated leukocytes enhance thymic stromal lymphopoietin production in a mouse air-pouch-type inflammation model. Inflammation. 39:1527–1537. 2016. View Article : Google Scholar : PubMed/NCBI

38 

Takai T: TSLP expression: cellular sources, triggers, and regulatory mechanisms. Allergol Int. 61:3–17. 2012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhang J, Zhao D, Na N, Li H, Miao B, Hong L and Huang Z: Renoprotective effect of erythropoietin via modulation of the STAT6/MAPK/NF-κB pathway in ischemia/reperfusion injury after renal transplantation. Int J Mol Med 41: 25-32, 2018.
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
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang J, Zhao D, Na N, Li H, Miao B, Hong L and Huang Z: Renoprotective effect of erythropoietin via modulation of the STAT6/MAPK/NF-κB pathway in ischemia/reperfusion injury after renal transplantation. Int J Mol Med 41: 25-32, 2018.
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
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