HGF/SF induces mesothelial cell migration and proliferation by autocrine and paracrine pathways.
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.
Warn
R
R
School of Biology, University of East Anglia, Norwich, NR4 7TJ, United Kingdom.
Harvey
P
P
Warn
A
A
Foley-Comer
A
A
Heldin
P
P
Versnel
M
M
Arakaki
N
N
Daikuhara
Y
Y
Laurent
G J
GJ
Herrick
S E
SE
Mutsaers
S E
SE
D000970:Antineoplastic Agents / Q000494:pharmacology; D019898:Autocrine Communication / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D019899:Paracrine Communication / Q000502:physiology*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D013498:Suramin / Q000494:pharmacology
D000970:Antineoplastic Agents; D013498:Suramin; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met