Gene therapy expressing amino-terminal truncated monocyte chemoattractant protein-1 prevents renal ischemia-reperfusion injury.
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.
Furuichi
Kengo
K
Department of Gastroenterology and Nephrology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
Wada
Takashi
T
Iwata
Yasunori
Y
Kitagawa
Kiyoki
K
Kobayashi
Ken-Ichi
K
Hashimoto
Hiroyuki
H
Ishiwata
Yoshiro
Y
Tomosugi
Naohisa
N
Mukaida
Naofumi
N
Matsushima
Kouji
K
Egashira
Kensuke
K
Yokoyama
Hitoshi
H
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
C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054390:Receptors, CCR2; D019707:Receptors, Chemokine