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

Autor: Naokatu Arakaki, Paraskevi Heldin, Alba Warn, Geoffrey J. Laurent, Sarah E. Herrick, Steven E. Mutsaers, R. M. Warn, Marjan A. Versnel, Adam J. Foley-Comer, Pascale Harvey, Yasushi Daikuhara
Rok vydání: 2001
Předmět:
Zdroj: Experimental cell research. 267(2)
ISSN: 0014-4827
Popis: Mesothelial repair differs from that of other epithelial-like surfaces as healing does not occur solely by centripetal in-growth of cells as a sheet from the wound margins. Mesothelial cells lose their cell-cell junctions, divide, and adopt a fibroblast-like morphology while scattering across and covering the wound surface. These features are consistent with a cellular response to hepatocyte growth factor/scatter factor (HGF/SF). In this study, we examined the ability of mesothelial cells to secrete HGF/SF and investigated its possible role as an autocrine regulator of mesothelial cell motility and proliferation. We found that human primary mesothelial cells expressed HGF/SF mRNA and secreted active HGF/SF into conditioned medium as determined by ELISA and in a scattering bioassay. These cells also expressed the HGF/SF receptor, Met, as shown by RT-PCR and by Western blot analysis and immunofluorescence. Incubation of mesothelial cells with neutralizing antibodies to HGF/SF decreased cell migration to 25% of controls, whereas addition of HGF/SF disrupted cell-cell junctions and induced scattering and enhanced mesothelial cell migration. Furthermore, HGF/SF showed a small but significant mitogenic effect on all mesothelial cell lines examined. In conclusion, HGF/SF is produced by mesothelial cells and induces both motility and proliferation of these cells. These data are consistent with HGF/SF playing an autocrine role in mesothelial healing.
Databáze: OpenAIRE