HGF-MSP chimera protects kidneys from ischemia-reperfusion injury.
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.
Xue
Feng
F
Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Isaka
Yoshitaka
Y
Takahara
Terumi
T
Imamura
Ryoichi
R
Suzuki
Chigure
C
Ichimaru
Naotsugu
N
Michieli
Paolo
P
Takahara
Shiro
S
D000818:Animals; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects*; D008297:Male; D020033:Protein Isoforms / Q000008:administration & dosage; D011518:Proto-Oncogene Proteins / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D016896:Treatment Outcome
D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor