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Original Research

Open Access

Inhibition of TRAF1 protects renal tubular epithelial cells against hypoxia/reoxygenation injury

  • Wei Yu1
  • Qifeng Mao2,3

1Department of Nephrology, Chongqing General Hospital, 400013 Chongqing, China

2Department of Clinical Laboratory, HwaMei Hospital, University of Chinese Academy of Sciences, 315010 Ningbo, Zhejiang Province, China

3Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, 315010 Ningbo, Zhejiang Province, China

DOI: 10.31083/jomh.2021.060 Vol.17,Issue 3,July 2021 pp.167-173

Submitted: 25 March 2021 Accepted: 15 June 2021

Published: 08 July 2021

*Corresponding Author(s): Qifeng Mao E-mail:

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Background and objective: This study aimed to explore the expression of TRAF1 in vitro kidney injury model, and the function mechanism of TRAF1 in the model growth and apoptosis.

Methods: After transfecting HK2 cells with short hair RNA (shRNA), shTRAF1 gene silencing model was established. The cells were divided into shRNA group and shNC group. For kidney injury model, we used hypoxia/reoxygenation to establish H/R cell lines. MTT assay was used to determine cell viability. PI/FITC staining was used to determine cell apoptosis. The genes expressions were determined by RT-qPCR and western blotting, respectively. The concentration of MDA, SOD, iNOS and LDH was determined by ELISA.

Results: The results of RT-qPCR and western blotting assay revealed that TRAF1 upregulated expression in AKI model cells. The results of MTT assay revealed that shRNA group exhibited significantly higher cell viability and lower cell apoptosis compared with the control group in H/R HK2 cells. In addition, TRAF1 downregulated expression inhibits oxidative stress response in H/R treated HK2 cell. Mechanically, TRAF1 deficiency protects HK2 cell via inhibiting p38-MAPK pathway.

Conclusions: Our study suggests that TRAF1 could be a target in kidney injury treatment.


TRAF1; AKI; Cell apoptosis; H/R injury; p38 MAPK pathway

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Wei Yu,Qifeng Mao. Inhibition of TRAF1 protects renal tubular epithelial cells against hypoxia/reoxygenation injury. Journal of Men's Health. 2021. 17(3);167-173.


[1] Lameire N, Kellum JA. Contrast-induced acute kidney injury and renal support for acute kidney injury: a KDIGO summary (Part 2). Critical Care. 2013; 17: 205.

[2] El-Zoghby ZM, Stegall MD, Lager DJ, Kremers WK, Amer H, Gloor JM, et al. Identifying Specific Causes of Kidney Allograft Loss. American Journal of Transplantation. 2009; 9: 527–535.

[3] Bagshaw SM, Bennett M, Haase M, Haase-Fielitz A, Egi M, Morimatsu H, et al. Plasma and urine neutrophil gelatinase-associated lipocalin in septic versus non-septic acute kidney injury in critical illness. Intensive Care Medicine. 2010; 36: 452–461.

[4] Morgan CJ, Gill PJ, Lam S, Joffe AR. Peri-operative interventions, but not inflammatory mediators, increase risk of acute kidney injury after cardiac surgery: a prospective cohort study. Intensive Care Medicine. 2013; 39: 934–941.

[5] Ricci Z, Romagnoli S. Acute Kidney Injury: Diagnosis and Classifica-tion in Adults and Children. Contributions to Nephrology. 2018; 193: 1–12.

[6] Deng F, Sharma I, Dai Y, Yang M, Kanwar YS. Myo-inositol oxygenase expression profile modulates pathogenic ferroptosis in the renal proximal tubule. Journal of Clinical Investigation. 2019; 129: 5033–5049.

[7] Martin-Sanchez D, Poveda J, Fontecha-Barriuso M, Ruiz-Andres O, Sanchez-Niño MD, Ruiz-Ortega M, et al. Targeting of regulated necrosis in kidney disease. Nefrología. 2018; 38: 125–135.

[8] Zhong X, He J, Zhang X, Li C, Tian X, Xia W, et al. UCP2 alleviates tubular epithelial cell apoptosis in lipopolysaccharide-induced acute kidney injury by decreasing ROS production. Biomedicine & Pharma-cotherapy. 2019; 115: 108914.

[9] Wang H, Peng X, Huang Y, Xiao Y, Wang Z, Zhan L. Propofol At-tenuates Hypoxia/Reoxygenation-Induced Apoptosis and Autophagy in HK-2 Cells by Inhibiting JNK Activation. Yonsei Medical Journal. 2019; 60: 1195.

[10] Bao H, Zhang Q, Liu X, Song Y, Li X, Wang Z, et al. Lithium targeting of AMPK protects against cisplatin-induced acute kidney injury by enhancing autophagy in renal proximal tubular epithelial cells. FASEB Journal. 2019; 33: 14370–14381.

[11] Son Y, Cheong Y, Kim N, Chung H, Kang DG, Pae H. Mitogen-Activated Protein Kinases and Reactive Oxygen Species: how can ROS Activate MAPK Pathways? Journal of Signal Transduction. 2011; 2011: 1–6.

[12] Ren Q, Guo F, Tao S, Huang R, Ma L, Fu P. Flavonoid fisetin alleviates kidney inflammation and apoptosis via inhibiting Src-mediated NF-kappaB p65 and MAPK signaling pathways in septic AKI mice. Biomed Pharmacother. 2020; 122: 109772.

[13] Yeda X, Shaoqing L, Yayi H, Bo Z, Huaxin W, Hong C, et al. Dexmedetomidine protects against renal ischemia and reperfusion injury by inhibiting the P38-MAPK/TXNIP signaling activation in streptozotocin induced diabetic rats. Acta Cirurgica Brasileira. 2017; 32: 429–439.

[14] Chen H, Huang R, Yu X, Ye Q, Pan L, Shao G, et al. Emodin protects against oxidative stress and apoptosis in HK-2 renal tubular epithelial cells after hypoxia/reoxygenation. Experimental and Therapeutic Medicine. 2017; 14: 447–452.

[15] Qi M, Zheng L, Qi Y, Han X, Xu Y, Xu L, et al. Dioscin attenuates renal ischemia/reperfusion injury by inhibiting the TLR4/MyD88 signaling pathway via up-regulation of HSP70. Pharmacological Research. 2015; 100: 341–352.

[16] Chen J, Wang W, Zhang Q, Li F, Lei T, Luo D, et al. Low molecular weight fucoidan against renal ischemia-reperfusion injury via inhibition of the MAPK signaling pathway. PLoS ONE. 2013; 8: e56224.

[17] Lee SY, Choi Y. TRAF1 and its biological functions. Advances in Experimental Medicine and Biology. 2007; 597: 25–31.

[18] Xu W, Zhang L, Zhang Y, Zhang K, Wu Y, Jin D. TRAF1 Exacerbates Myocardial Ischemia Reperfusion Injury via ASK1–JNK/p38 Signal-ing. Journal of the American Heart Association. 2019; 8: e012575.

[19] Bin W, Ming X, Wen-Xia C. TRAF1 meditates lipopolysaccharide-induced acute lung injury by up regulating JNK activation. Biochemical and Biophysical Research Communications. 2019; 511: 49–56.

[20] Huang X, Gao Y, Qin J, Lu S. MiR-214 down-Regulation Promoted Hypoxia/Reoxygenation-Induced Hepatocyte Apoptosis through TRAF1/ASK1/JNK Pathway. Digestive Diseases and Sciences. 2019; 64: 1217–1225.

[21] Rajandram R, Bennett NC, Wang Z, Perry-Keene J, Vesey DA, Johnson DW, et al. Patient samples of renal cell carcinoma show reduced expression of TRAF1 compared with normal kidney and functional studies in vitro indicate TRAF1 promotes apoptosis: potential for targeted therapy. Pathology. 2012; 44: 453–459.

[22] Rajandram R, Yap NY, Pailoor J, Razack AHA, Ng KL, Ong TA, et al. Tumour necrosis factor receptor-associated factor-1 (TRAF-1) expression is increased in renal cell carcinoma patient serum but decreased in cancer tissue compared with normal: potential biomarker significance. Pathology. 2014; 46: 518–522.

[23] Dong L, Yu L, Li H, Shi L, Luo Z, Zhao H, et al. An NAD+−Dependent Deacetylase SIRT7 Promotes HCC Development through Deacetyla-tion of USP39. IScience. 2020; 23: 101351.

[24] Dong L, Yu L, Bai C, Liu L, Long H, Shi L, et al. USP27-mediated Cyclin E stabilization drives cell cycle progression and hepatocellular tumorigenesis. Oncogene. 2018; 37: 2702–2713.

[25] Yu L, Dong L, Wang Y, Liu L, Long H, Li H, et al. Reversible regulation of SATB1 ubiquitination by USP47 and SMURF2 mediates colon cancer cell proliferation and tumor progression. Cancer Letters. 2019; 448: 40–51.

[26] Bradley JR, Pober JS. Tumor necrosis factor receptor-associated factors (TRAFs). Oncogene. 2001; 20: 6482–6491.

[27] Chaudhary PM, Eby MT, Jasmin A, Kumar A, Liu L, Hood L. Activation of the NF-kappaB pathway by caspase 8 and its homologs. Oncogene. 2000; 19: 4451–4460.

[28] Lu Y, Li Z, Jiang D, Wang L, Zhang Y, Chen K, et al. TRAF1 is a critical regulator of cerebral ischaemia-reperfusion injury and neuronal death. Nature Communications. 2013; 4: 2852.

[29] Zhang X, Zhang R, Huang L, Wang P, Zhang Y, Jiang D, et al. TRAF1 is a key mediator for hepatic ischemia/reperfusion injury. Cell Death & Disease. 2014; 5: e1467.

[30] Wang Q, Gao G, Zhang T, Yao K, Chen H, Park MH, et al. TRAF1 is Critical for Regulating the BRAF/MEK/ERK Pathway in Non-Small Cell Lung Carcinogenesis. Cancer Research. 2018; 78: 3982–3994.

[31] Micheau O, Tschopp J. Induction of TNF receptor i-mediated apoptosis via two sequential signaling complexes. Cell. 2003; 114: 181–190.

[32] Song Z, Jin R, Yu S, Rivet JJ, Smyth SS, Nanda A, et al. CD40 is essential in the upregulation of TRAF proteins and NF-kappaB-dependent proinflammatory gene expression after arterial injury. PLoS ONE. 2011; 6: e23239.

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