PMID- 27752902 OWN - NLM STAT- MEDLINE DCOM- 20170330 LR - 20181113 IS - 1993-1352 (Electronic) IS - 1672-0733 (Linking) VI - 36 IP - 5 DP - 2016 Oct TI - Small interfering RNA targeting TNF-alpha gene significantly attenuates renal ischemia-reperfusion injury in mice. PG - 634-638 LID - 10.1007/s11596-016-1638-z [doi] AB - Tumor necrosis factor-alpha (TNF-alpha) has been found to be centrally involved in the development of ischemia-reperfusion injury (IRI)-induced inflammation and apoptosis. Knockdown of TNF-alpha 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-alpha siRNA was administered intravenously to silence the expression of TNF-alpha. 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-alpha siRNA resulted in significant knockdown of TNF-alpha 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-alpha 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-alpha by specific siRNA can significantly reduce renal IRI and protect mice against lethal kidney ischemia, highlighting the potential for siRNA-based clinical therapy. FAU - Hou, Ling AU - Hou L AD - Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. FAU - Chen, Gang AU - Chen G AD - Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. gchen@tjh.tjmu.edu.cn. AD - Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, 430030, China. gchen@tjh.tjmu.edu.cn. AD - Key Laboratory of Organ Transplantation, Ministry of Public Health, Wuhan, 430030, China. gchen@tjh.tjmu.edu.cn. FAU - Feng, Biao AU - Feng B AD - Departments of Surgery, Microbiology and Immunology, and Pathology, University of Western Ontario, London, Canada. FAU - Zhang, Xu-Sheng AU - Zhang XS AD - Departments of Surgery, Microbiology and Immunology, and Pathology, University of Western Ontario, London, Canada. FAU - Zheng, Xiu-Fen AU - Zheng XF AD - Departments of Surgery, Microbiology and Immunology, and Pathology, University of Western Ontario, London, Canada. FAU - Xiang, Ying AU - Xiang Y AD - Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. AD - Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, 430030, China. AD - Key Laboratory of Organ Transplantation, Ministry of Public Health, Wuhan, 430030, China. FAU - Zhao, Guang-Yuan AU - Zhao GY AD - Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. FAU - Min, Wei-Ping AU - Min WP AD - Departments of Surgery, Microbiology and Immunology, and Pathology, University of Western Ontario, London, Canada. LA - eng PT - Journal Article DEP - 20161018 PL - China TA - J Huazhong Univ Sci Technolog Med Sci JT - Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban JID - 101169627 RN - 0 (RNA, Small Interfering) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Animals MH - Apoptosis MH - Disease Models, Animal MH - Genetic Therapy MH - Humans MH - Inflammation/*genetics/pathology/therapy MH - Kidney/drug effects/injuries/pathology MH - Mice MH - RNA, Small Interfering/*administration & dosage/genetics MH - Reperfusion Injury/*genetics/pathology/therapy MH - Tumor Necrosis Factor-alpha/antagonists & inhibitors/*genetics OTO - NOTNLM OT - ischemia-reperfusion injury OT - kidney OT - small interfering RNA OT - tumor necrosis factor-alpha EDAT- 2016/10/19 06:00 MHDA- 2017/03/31 06:00 CRDT- 2016/10/19 06:00 PHST- 2016/07/02 00:00 [received] PHST- 2016/08/22 00:00 [revised] PHST- 2016/10/19 06:00 [pubmed] PHST- 2017/03/31 06:00 [medline] PHST- 2016/10/19 06:00 [entrez] AID - 10.1007/s11596-016-1638-z [pii] AID - 10.1007/s11596-016-1638-z [doi] PST - ppublish SO - J Huazhong Univ Sci Technolog Med Sci. 2016 Oct;36(5):634-638. doi: 10.1007/s11596-016-1638-z. Epub 2016 Oct 18.