HGF/SF induces mesothelial cell migration and proliferation by autocrine and paracrine pathways

Mesothelial repair differs from that of other epithelial-like surfaces as h ealing does not occur solely by centripetal in-growth of cells as a sheet f rom the wound margins. Mesothelial cells lose their cell-cell junctions, di vide, and adopt a fibroblast-like morphology while scattering across and co vering the wound surface. These features are consistent with a cellular res ponse to hepatocyte growth factor/scatter factor (HGF/SF). In this study, w e examined the ability of mesothelial cells to secrete HGF/SF and investiga ted its possible role as an autocrine regulator of mesothelial cell motilit y and proliferation. We found that human primary mesothelial cells expresse d HGF/SF mRNA and secreted active HGF/SF into conditioned medium as determi ned by ELISA and in a scattering bioassay. These cells also expressed the H GF/SF receptor, Met, as shown by RT-PCR and by Western blot analysis and im munofluorescence. Incubation of mesothelial cells with neutralizing antibod ies to HGF/SF decreased cell migration to 25% of controls, whereas addition of HGF/SF disrupted cell-cell junctions and induced scattering and enhance d mesothelial cell migration. Furthermore, HGF/SF showed a small but signif icant mitogenic effect on all mesothelial cell lines examined. In conclusio n, HGF/SF is produced by mesothelial cells and induces both motility and pr oliferation of these cells. These data are consistent with HGF/SF playing a n autocrine role in mesothelial healing. (C) 2001 Academic Press.