HGF-MSP chimera protects kidneys from ischemia-reperfusion injury

Feng Xue, Yoshitaka Isaka, Terumi Takahara, Ryoichi Imamura, Chigure Suzuki, Naotsugu Ichimaru, Paolo Michieli, Shiro Takahara

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)451-456
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume363
Issue number2
DOIs
Publication statusPublished - Nov 16 2007

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Keywords

  • Apoptosis
  • Hypoxia
  • Ischemia-reperfusion
  • Kidney
  • Macrophage

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Xue, F., Isaka, Y., Takahara, T., Imamura, R., Suzuki, C., Ichimaru, N., Michieli, P., & Takahara, S. (2007). HGF-MSP chimera protects kidneys from ischemia-reperfusion injury. Biochemical and Biophysical Research Communications, 363(2), 451-456. https://doi.org/10.1016/j.bbrc.2007.05.229