H. Ihn et K. Tamaki, Oncostatin M stimulates the growth of dermal fibroblasts via a mitogen-activated protein kinase-dependent pathway, J IMMUNOL, 165(4), 2000, pp. 2149-2155
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.