Gene therapy expressing amino-terminal truncated monocyte chemoattractant protein-1 prevents renal ischemia-reperfusion injury

Kengo Furuichi, Takashi Wada, Yasunori Iwata, Kiyoki Kitagawa, Ken Ichi Kobayashi, Hiroyuki Hashimoto, Yoshiro Ishiwata, Naohisa Tomosugi, Naofumi Mukaida, Kouji Matsushima, Kensuke Egashira, Hitoshi Yokoyama

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82 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1066-1071
Number of pages6
JournalJournal of the American Society of Nephrology
Volume14
Issue number4
DOIs
Publication statusPublished - Apr 1 2003

All Science Journal Classification (ASJC) codes

  • Nephrology

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    Furuichi, K., Wada, T., Iwata, Y., Kitagawa, K., Kobayashi, K. I., Hashimoto, H., Ishiwata, Y., Tomosugi, N., Mukaida, N., Matsushima, K., Egashira, K., & Yokoyama, H. (2003). Gene therapy expressing amino-terminal truncated monocyte chemoattractant protein-1 prevents renal ischemia-reperfusion injury. Journal of the American Society of Nephrology, 14(4), 1066-1071. https://doi.org/10.1097/01.ASN.0000059339.14780.E4