An HGF-MSP chimera disassociates the trophic properties of scatter factors from their pro-invasive activity

Paolo Michieli, Silvia Cavassa, Cristina Basilico, Annarita De Luca, Massimiliano Mazzone, Cinzia Asti, Riccardo Chiusaroli, Mario Guglielmi, Paola Bossù, Francesco Colotta, Gianfranco Caselli, Paolo M. Comoglio

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish
Pages (from-to)488-495
Number of pages8
JournalNature Biotechnology
Volume20
Issue number5
DOIs
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Microbiology

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