title: Gene therapy expressing amino-terminal truncated monocyte chemoattractant protein-1 prevents renal ischemia-reperfusion injury.
abstract: Ischemia-reperfusion is closely associated with tissue damage in various organs, including kidney. Despite clinical investigations, useful therapy for renal ischemia-reperfusion injury is not available so far. This study evaluated therapeutic effects of gene therapy expressing an amino-terminal deletion mutant of MCP-1 called 7ND to inhibit monocyte chemoattractant protein (MCP)-1/CCR2 signaling in vivo on renal ischemia-reperfusion injury. 7ND gene was transferred into the femoral muscle of Balb/c mice. Renal artery and vein of the left kidney were occluded with a vascular clamp for 60 min. A large number of infiltrated cells were observed, as was marked acute tubular necrosis in outer medulla after renal ischemia-reperfusion injury in control mice, while these lesions were significantly decreased in 7ND gene-transfected mice. Macrophages in the interstitial region, most of which were CCR2-positive, were markedly decreased in 7ND gene-transfected mice after reperfusion. Although macrophages infiltrated around MCP-1-positive cells in control mice, the smaller number of F4/80-positive cells could infiltrate into the neighbor of MCP-1-positive cells in 7ND-treated mice. These results provide evidence that gene therapy by 7ND is potentially a powerful therapeutic approach to inhibit MCP-1/CCR2 signaling, resulting in rescue from renal ischemia-reperfusion injury.
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Furuichi
authors.forename: Takashi
authors.initials: T
authors.lastname: Wada
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Iwata
authors.forename: Kiyoki
authors.initials: K
authors.lastname: Kitagawa
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Ishiwata
authors.forename: Naohisa
authors.initials: N
authors.lastname: Tomosugi
authors.forename: Naofumi
authors.initials: N
authors.lastname: Mukaida
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Kensuke
authors.initials: K
authors.lastname: Egashira
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D017353:Gene Deletion; D015316:Genetic Therapy / Q000379:methods*; D007674:Kidney Diseases / Q000235:genetics / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics / Q000502:physiology; D015427:Reperfusion Injury / Q000235:genetics / Q000517:prevention & control*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054390:Receptors, CCR2; D019707:Receptors, Chemokine