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 i mplicated 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, w e have investigated the mechanism of the growth regulation of dermal fibrob lasts by OSM, OSM stimulates the mitogenesis of dermal fibroblasts in a dos e-dependent manner. This effect was completely blocked by anti-OSM IgG, but not by anti-IL-6 IgG. Furthermore, OSM induction was abolished by genistei n, 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 ph osphorylated MAP kinase (Thr(202)/Tyr(204)) showed that OSM induces phospho rylation of MAP kinase in dermal fibroblasts. Furthermore, transient transf ection of the dominant-negative mutant MAP kinase into dermal fibroblasts a bolished the OSM induction. These results strongly suggest that OSM stimula tes the growth of dermal fibroblasts via a MAP kinase-dependent pathway.