TY - JOUR
T1 - An HGF-MSP chimera disassociates the trophic properties of scatter factors from their pro-invasive activity
AU - Michieli, Paolo
AU - Cavassa, Silvia
AU - Basilico, Cristina
AU - De Luca, Annarita
AU - Mazzone, Massimiliano
AU - Asti, Cinzia
AU - Chiusaroli, Riccardo
AU - Guglielmi, Mario
AU - Bossù, Paola
AU - Colotta, Francesco
AU - Caselli, Gianfranco
AU - Comoglio, Paolo M.
PY - 2002
Y1 - 2002
N2 - Hepatocyte growth factor (HGF) and macrophage-stimulating protein (MSP) have an intrinsic dual nature: they are trophic cytokines preventing apoptosis on one side and scatter factors promoting invasion on the other. For therapeutic use, their anti-apoptotic activity must be separated from their pro-invasive activity. To this end, we engineered chimeric factors containing selected functional domains of HGF and/or MSP in different combinations, and tested their biological activity. Here we present a chimeric cytokine derived from the α-chains of HGF and MSP, named Metron factor 1 for its ability to concomitantly activate the HGF receptor (Met) and the MSP receptor (Ron). We provide evidence that Metron factor 1 prevents apoptosis and stimulates cell proliferation at nanomolar concentrations, but is devoid of any pro-invasive activity. In an in vivo murine model of drug-induced nephrotoxicity, intravenous injection of recombinant Metron factor 1 prevented renal damage and preserved tubular integrity.
AB - Hepatocyte growth factor (HGF) and macrophage-stimulating protein (MSP) have an intrinsic dual nature: they are trophic cytokines preventing apoptosis on one side and scatter factors promoting invasion on the other. For therapeutic use, their anti-apoptotic activity must be separated from their pro-invasive activity. To this end, we engineered chimeric factors containing selected functional domains of HGF and/or MSP in different combinations, and tested their biological activity. Here we present a chimeric cytokine derived from the α-chains of HGF and MSP, named Metron factor 1 for its ability to concomitantly activate the HGF receptor (Met) and the MSP receptor (Ron). We provide evidence that Metron factor 1 prevents apoptosis and stimulates cell proliferation at nanomolar concentrations, but is devoid of any pro-invasive activity. In an in vivo murine model of drug-induced nephrotoxicity, intravenous injection of recombinant Metron factor 1 prevented renal damage and preserved tubular integrity.
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U2 - 10.1038/nbt0502-488
DO - 10.1038/nbt0502-488
M3 - Article
C2 - 11981563
AN - SCOPUS:0036246707
VL - 20
SP - 488
EP - 495
JO - Biotechnology
JF - Biotechnology
SN - 1087-0156
IS - 5
ER -