1. HGF–MSP chimera protects kidneys from ischemia–reperfusion injury
- Author
-
Xue, Feng, Isaka, Yoshitaka, Takahara, Terumi, Imamura, Ryoichi, Suzuki, Chigure, Ichimaru, Naotsugu, Michieli, Paolo, and Takahara, Shiro
- Subjects
- *
BIOLOGY , *BIOPHYSICS , *BIOCHEMISTRY , *LIFE sciences - Abstract
Abstract: 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. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF