Oncostatin M stimulates the growth of dermal fibroblasts via a mitogen-activated protein kinase-dependent pathway.
Oncostatin M (OSM), a member of the hemopoietic cytokine family, has been implicated in the process of fibrosis and dermal wound healing. As a part of an ongoing study of the mechanisms of fibrosis and dermal wound healing, we have investigated the mechanism of the growth regulation of dermal fibroblasts by OSM. OSM stimulates the mitogenesis of dermal fibroblasts in a dose-dependent manner. This effect was completely blocked by anti-OSM IgG, but not by anti-IL-6 IgG. Furthermore, OSM induction was abolished by genistein, a tyrosine kinase inhibitor, or by PD98059, a specific mitogen-activated protein (MAP) kinase pathway inhibitor, but not by calphostin C, a protein kinase C inhibitor. Immunoblotting analysis using a specific Ab against phosphorylated MAP kinase (Thr202/Tyr204) showed that OSM induces phosphorylation of MAP kinase in dermal fibroblasts. Furthermore, transient transfection of the dominant-negative mutant MAP kinase into dermal fibroblasts abolished the OSM induction. These results strongly suggest that OSM stimulates the growth of dermal fibroblasts via a MAP kinase-dependent pathway.
Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan. IN-DER@h.u-tokyo.ac.jp
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D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology; D002478:Cells, Cultured; D004247:DNA / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D005822:Genetic Vectors / Q000138:chemical synthesis; D019833:Genistein / Q000494:pharmacology; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D053683:Oncostatin M; D010455:Peptides / Q000037:antagonists & inhibitors / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
D004791:Enzyme Inhibitors; D006133:Growth Substances; C508351:OSM protein, human; D010455:Peptides; D053683:Oncostatin M; D014443:Tyrosine; D004247:DNA; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D019950:Mitogen-Activated Protein Kinase 1