title: Small interfering RNA targeting TNF-α gene significantly attenuates renal ischemia-reperfusion injury in mice.
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.
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Hou
authors.affiliation: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. gchen@tjh.tjmu.edu.cn.|Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, 430030, China. gchen@tjh.tjmu.edu.cn.|Key Laboratory of Organ Transplantation, Ministry of Public Health, Wuhan, 430030, China. gchen@tjh.tjmu.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Departments of Surgery, Microbiology and Immunology, and Pathology, University of Western Ontario, London, Canada.
authors.forename: Biao
authors.initials: B
authors.lastname: Feng
authors.affiliation: Departments of Surgery, Microbiology and Immunology, and Pathology, University of Western Ontario, London, Canada.
authors.forename: Xu-Sheng
authors.initials: XS
authors.lastname: Zhang
authors.affiliation: Departments of Surgery, Microbiology and Immunology, and Pathology, University of Western Ontario, London, Canada.
authors.forename: Xiu-Fen
authors.initials: XF
authors.lastname: Zheng
authors.affiliation: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.|Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, 430030, China.|Key Laboratory of Organ Transplantation, Ministry of Public Health, Wuhan, 430030, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Guang-Yuan
authors.initials: GY
authors.lastname: Zhao
authors.affiliation: Departments of Surgery, Microbiology and Immunology, and Pathology, University of Western Ontario, London, Canada.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Min
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D015316:Genetic Therapy; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D007668:Kidney / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D051379:Mice; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D015427:Reperfusion Injury / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha
keywords: ischemia-reperfusion injury; kidney; small interfering RNA; tumor necrosis factor-alpha