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Small interfering RNA targeting TNF-α gene significantly attenuates renal ischemia-reperfusion injury in mice

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Abstract

Tumor necrosis factor-alpha (TNF-α) has been found to be centrally involved in the development of ischemia-reperfusion injury (IRI)-induced inflammation and apoptosis. Knockdown of TNF-α gene using small interfering RNA (siRNA) may protect renal IRI. Renal IRI was induced in mice by clamping the left renal pedicle for 25 or 35 min. TNF-α siRNA was administered intravenously to silence the expression of TNF-α. The therapeutic effects of siRNA were evaluated in terms of renal function, histological examination, and overall survival following lethal IRI. A single systemic injection of TNF-α siRNA resulted in significant knockdown of TNF-α expression in ischemia-reperfusion injured kidney. In comparison with control mice, levels of BUN and serum creatinine were significantly reduced in mice treated with siRNA. Pathological examination demonstrated that tissue damage caused by IRI was markedly reduced as a result of TNF-α siRNA treatment. Furthermore, survival experiments showed that nearly 90% of control mice died from lethal IRI, whereas more than 50% of siRNApretreated mice survived until the end of the eight-day observation period. We have demonstrated for the first time that silencing TNF-α by specific siRNA can significantly reduce renal IRI and protect mice against lethal kidney ischemia, highlighting the potential for siRNA-based clinical therapy.

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Authors and Affiliations

  1. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Ling Hou  (侯 凌)

  2. Departments of Surgery, Microbiology and Immunology, and Pathology, University of Western Ontario, London, Canada

    Biao Feng  (冯 彪), Xu-sheng Zhang  (张旭升), Xiu-fen Zheng  (郑秀芬) & Wei-Ping Min  (闵卫平)

  3. Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Gang Chen  (陈 刚), Ying Xiang  (向 莹) & Guang-yuan Zhao  (赵光远)

  4. Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, 430030, China

    Gang Chen  (陈 刚) & Ying Xiang  (向 莹)

  5. Key Laboratory of Organ Transplantation, Ministry of Public Health, Wuhan, 430030, China

    Gang Chen  (陈 刚) & Ying Xiang  (向 莹)

Authors
  1. Ling Hou  (侯 凌)
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  2. Gang Chen  (陈 刚)
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  3. Biao Feng  (冯 彪)
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  4. Xu-sheng Zhang  (张旭升)
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  5. Xiu-fen Zheng  (郑秀芬)
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  6. Ying Xiang  (向 莹)
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  7. Guang-yuan Zhao  (赵光远)
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  8. Wei-Ping Min  (闵卫平)
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Correspondence to Gang Chen  (陈 刚).

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Hou, L., Chen, G., Feng, B. et al. Small interfering RNA targeting TNF-α gene significantly attenuates renal ischemia-reperfusion injury in mice. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 36, 634–638 (2016). https://doi.org/10.1007/s11596-016-1638-z

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  • DOI: https://doi.org/10.1007/s11596-016-1638-z

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