HGF-MSP chimera protects kidneys from ischemia-reperfusion injury

作者：Xue, Feng; Isaka, Yoshitaka^*; Takahara, Terumi; Imamura, Ryoichi; Suzuki, Chigure; Ichimaru, Naotsugu; Michieli, Paolo; Takahara, Shiro

来源：Biochemical and Biophysical Research Communications, 2007, 363(2): 451-456.

DOI：10.1016/j.bbrc.2007.05.229

• ischemia-reperfusion
• hypoxia
• apoptosis
• kidney
• macrophage

Renal ischemia-reperfusion (I/R) injury is inevitable in transplantation and is related to long-term graft function. MF-1, a bifunctional hepatocyte growth factor (HGF)-macrophage-stimulating protein (MSP) (HGF-MSP) chimera was recently reported to prevent apoptosis. We therefore hypothesized that treatment with MF-1 would protect kidneys from I/R injury by inhibiting tubular epithelial apoptosis. MF-1 directly guarded cultured proximal tubular epithelial cells from hypoxia-induced necrosis and apoptosis in vitro. In addition, the therapeutic effects of MF-1 were evaluated using a rat I/R injury model in vivo. Saline-treated kidneys had increased creatinine and BUN, and exhibited tubular epithelial apoptosis with activated caspase 3 expression. In contrast, MF-1 treatment up-regulated Akt phosphorylation, and inhibited caspase 3 activation and tubular apoptosis, thereby ameliorating renal dysfunction. Of particular interest is that macrophage infiltration was suppressed in the MF-1-treated kidney. In conclusion, we identified a novel therapeutic approach using MF-1 to protect kidneys from I/R injury.

• 出版日期2007-11-16
• 单位上海交通大学