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  • Title: An HGF-MSP chimera disassociates the trophic properties of scatter factors from their pro-invasive activity.
    Author: Michieli P, Cavassa S, Basilico C, De Luca A, Mazzone M, Asti C, Chiusaroli R, Guglielmi M, Bossù P, Colotta F, Caselli G, Comoglio PM.
    Journal: Nat Biotechnol; 2002 May; 20(5):488-95. PubMed ID: 11981563.
    Abstract:
    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 alpha-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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