Oncostatin M is a Mitogen for Rabbit Vascular Smooth Muscle Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS 1993-02, Vol.90 (3), p.823-827
• Main Authors: Grove, R I, Eberhardt, C, Abid, S, Mazzucco, C, Liu, J, Kiener, P, Todaro, G, Shoyab, M
• Format: Article
• Language: English
• Subjects: Animals; Aorta - cytology; Biological and medical sciences; Cell cycle, cell proliferation; Cell Division - drug effects; Cell growth; Cell physiology; Cells, Cultured; Cellular biology; Circulatory system; Cytokines - pharmacology; Diglycerides; DNA; Fundamental and applied biological sciences. Psychology; Immediate early genes; Inositol phosphates; Lesions; Liver cells; Macrophages; Medical research; Mitogens - pharmacology; Molecular and cellular biology; Muscle Development; Muscle Proteins - metabolism; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - growth & development; Oncostatin M; Peptides - pharmacology; Phosphorylation; Protein-Tyrosine Kinases - metabolism; Rabbits; Vanadates
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.3.823

The growth regulatory protein oncostatin M was initially discovered in macrophage-conditioned medium. We investigated the effects of oncostatin M on cultured rabbit aorta smooth muscle cells (SMCs) and found that the peptide stimulated an increase in the incorporation of [H]thymidine into DNA. The magnitude of the stimulation was dependent on oncostatin M concentration and SMC confluency. In subconfluent cultures, 1-2 nM stimulated 4- to 5-fold increases in DNA synthesis after 20 hr. Other structurally related cytokines (granulocyte colony-stimulating factor, leukemia inhibitory factor, interleukin 6, ciliary neurotrophic factor) did not affect SMC DNA synthesis. After 5 or 8 days, oncostatin M caused a doubling in SMC number and also induced a transformed phenotype. The combination of oncostatin M and platelet-derived growth factor for 8 days resulted in a 4-fold increase in cell number, approximately the same increase in cell number as induced by the addition of 10% fetal calf serum. Further investigation suggested that the mitogenic effect of oncostatin M was in part due to tyrosine kinase activation. Within 1-2 min, the factor increased phosphotyrosine levels of several SMC proteins. In addition, detectable increases in diacylglycerol levels occurred within 2-5 min, reached 50% above control by 30 min, and remained elevated through 45 min of incubation with oncostatin M. SMC inositol phosphate levels were also elevated within 2 min and then returned to near control values by 20 min. Within 30 min, oncostatin M induced expression of the immediate-early gene EGR-1. These data indicate that oncostatin M may be an important, naturally occurring mitogen for vascular SMCs.