Gene therapy expressing amino-terminal truncated monocyte chemoattractant protein-1 prevents renal ischemia-reperfusion injury
Gene therapy expressing amino-terminal truncated monocyte chemoattractant protein-1 prevents renal ischemia-reperfusion injury
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DOI：
10.1097/01.asn.0000059339.14780.e4
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发表时间：
2003-04-01
影响因子：
13.6
通讯作者：
Yokoyama, H
中科院分区：
文献类型：
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作者：
Furuichi, K;Wada, T;Yokoyama, H
缺血再灌注与包括肾脏在内的多种器官的组织损伤密切相关。尽管有临床研究，但迄今为止对肾缺血再灌注损伤的有效治疗尚不存在。本研究评价了表达MCP-1氨基端缺失突变体7 ND的基因治疗对肾缺血再灌注损伤的治疗作用，以抑制体内单核细胞趋化蛋白（MCP）-1/CCR2信号转导。将7 ND基因导入Balb/c小鼠股肌。用血管钳阻断左肾动脉和静脉60 min。对照组小鼠肾缺血再灌注损伤后，肾外髓质可见大量浸润细胞和明显的急性肾小管坏死，而7 ND基因转染组这些病变明显减轻。再灌注后，7 ND基因转染小鼠间质区的巨噬细胞明显减少，其中大部分为CCR 2阳性。对照组小鼠MCP-1阳性细胞周围有巨噬细胞浸润，而7 ND组小鼠MCP-1阳性细胞周围有少量F4/80阳性细胞浸润。这些结果提供了证据表明，通过7 ND的基因治疗是潜在的一种强有力的治疗方法，以抑制MCP-1/CCR 2信号转导，导致从肾缺血-再灌注损伤的救援。
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.