Abstract
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 [3H]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.
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- BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
- Bazan J. F. Neuropoietic cytokines in the hematopoietic fold. Neuron. 1991 Aug;7(2):197–208. doi: 10.1016/0896-6273(91)90258-2. [DOI] [PubMed] [Google Scholar]
- Benditt E. P., Barrett T., McDougall J. K. Viruses in the etiology of atherosclerosis. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6386–6389. doi: 10.1073/pnas.80.20.6386. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Besterman J. M., Duronio V., Cuatrecasas P. Rapid formation of diacylglycerol from phosphatidylcholine: a pathway for generation of a second messenger. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6785–6789. doi: 10.1073/pnas.83.18.6785. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown T. J., Lioubin M. N., Marquardt H. Purification and characterization of cytostatic lymphokines produced by activated human T lymphocytes. Synergistic antiproliferative activity of transforming growth factor beta 1, interferon-gamma, and oncostatin M for human melanoma cells. J Immunol. 1987 Nov 1;139(9):2977–2983. [PubMed] [Google Scholar]
- Brown T. J., Rowe J. M., Liu J. W., Shoyab M. Regulation of IL-6 expression by oncostatin M. J Immunol. 1991 Oct 1;147(7):2175–2180. [PubMed] [Google Scholar]
- Campbell G. R., Campbell J. H. Smooth muscle phenotypic changes in arterial wall homeostasis: implications for the pathogenesis of atherosclerosis. Exp Mol Pathol. 1985 Apr;42(2):139–162. doi: 10.1016/0014-4800(85)90023-1. [DOI] [PubMed] [Google Scholar]
- Christy B., Nathans D. Functional serum response elements upstream of the growth factor-inducible gene zif268. Mol Cell Biol. 1989 Nov;9(11):4889–4895. doi: 10.1128/mcb.9.11.4889. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cunningham M. J., Pasternak R. C. The potential role of viruses in the pathogenesis of atherosclerosis. Circulation. 1988 May;77(5):964–966. doi: 10.1161/01.cir.77.5.964. [DOI] [PubMed] [Google Scholar]
- Dean N. M., Moyer J. D. Metabolism of inositol bis-, tris-, tetrakis- and pentakis-phosphates in GH3 cells. Biochem J. 1988 Mar 1;250(2):493–500. doi: 10.1042/bj2500493. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eghbali M., Tomek R., Sukhatme V. P., Woods C., Bhambi B. Differential effects of transforming growth factor-beta 1 and phorbol myristate acetate on cardiac fibroblasts. Regulation of fibrillar collagen mRNAs and expression of early transcription factors. Circ Res. 1991 Aug;69(2):483–490. doi: 10.1161/01.res.69.2.483. [DOI] [PubMed] [Google Scholar]
- Faggiotto A., Ross R., Harker L. Studies of hypercholesterolemia in the nonhuman primate. I. Changes that lead to fatty streak formation. Arteriosclerosis. 1984 Jul-Aug;4(4):323–340. doi: 10.1161/01.atv.4.4.323. [DOI] [PubMed] [Google Scholar]
- Gearing D. P., Comeau M. R., Friend D. J., Gimpel S. D., Thut C. J., McGourty J., Brasher K. K., King J. A., Gillis S., Mosley B. The IL-6 signal transducer, gp130: an oncostatin M receptor and affinity converter for the LIF receptor. Science. 1992 Mar 13;255(5050):1434–1437. doi: 10.1126/science.1542794. [DOI] [PubMed] [Google Scholar]
- Gerrity R. G. The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions. Am J Pathol. 1981 May;103(2):181–190. [PMC free article] [PubMed] [Google Scholar]
- Grotendorst G. R., Chang T., Seppä H. E., Kleinman H. K., Martin G. R. Platelet-derived growth factor is a chemoattractant for vascular smooth muscle cells. J Cell Physiol. 1982 Nov;113(2):261–266. doi: 10.1002/jcp.1041130213. [DOI] [PubMed] [Google Scholar]
- Grove R. I., Mazzucco C., Allegretto N., Kiener P. A., Spitalny G., Radka S. F., Shoyab M., Antonaccio M., Warr G. A. Macrophage-derived factors increase low density lipoprotein uptake and receptor number in cultured human liver cells. J Lipid Res. 1991 Dec;32(12):1889–1897. [PubMed] [Google Scholar]
- Grove R. I., Schimmel S. D. Effects of 12-O-tetradecanoylphorbol 13-acetate on glycerolipid metabolism in cultured myoblasts. Biochim Biophys Acta. 1982 May 13;711(2):272–280. doi: 10.1016/0005-2760(82)90036-4. [DOI] [PubMed] [Google Scholar]
- Hansson G. K., Jonasson L., Seifert P. S., Stemme S. Immune mechanisms in atherosclerosis. Arteriosclerosis. 1989 Sep-Oct;9(5):567–578. doi: 10.1161/01.atv.9.5.567. [DOI] [PubMed] [Google Scholar]
- Higashiyama S., Abraham J. A., Miller J., Fiddes J. C., Klagsbrun M. A heparin-binding growth factor secreted by macrophage-like cells that is related to EGF. Science. 1991 Feb 22;251(4996):936–939. doi: 10.1126/science.1840698. [DOI] [PubMed] [Google Scholar]
- Horn D., Fitzpatrick W. C., Gompper P. T., Ochs V., Bolton-Hansen M., Zarling J., Malik N., Todaro G. J., Linsley P. S. Regulation of cell growth by recombinant oncostatin M. Growth Factors. 1990;2(2-3):157–165. doi: 10.3109/08977199009071502. [DOI] [PubMed] [Google Scholar]
- Jonasson L., Holm J., Skalli O., Bondjers G., Hansson G. K. Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque. Arteriosclerosis. 1986 Mar-Apr;6(2):131–138. doi: 10.1161/01.atv.6.2.131. [DOI] [PubMed] [Google Scholar]
- Libby P., Salomon R. N., Payne D. D., Schoen F. J., Pober J. S. Functions of vascular wall cells related to development of transplantation-associated coronary arteriosclerosis. Transplant Proc. 1989 Aug;21(4):3677–3684. [PubMed] [Google Scholar]
- Linsley P. S., Bolton-Hanson M., Horn D., Malik N., Kallestad J. C., Ochs V., Zarling J. M., Shoyab M. Identification and characterization of cellular receptors for the growth regulator, oncostatin M. J Biol Chem. 1989 Mar 15;264(8):4282–4289. [PubMed] [Google Scholar]
- Liu J. W., Lacy J., Sukhatme V. P., Coleman D. L. Granulocyte-macrophage colony-stimulating factor induces transcriptional activation of Egr-1 in murine peritoneal macrophages. J Biol Chem. 1991 Mar 25;266(9):5929–5933. [PubMed] [Google Scholar]
- Liu J., Clegg C. H., Shoyab M. Regulation of EGR-1, c-jun, and c-myc gene expression by oncostatin M. Cell Growth Differ. 1992 May;3(5):307–313. [PubMed] [Google Scholar]
- Malik N., Graves D., Shoyab M., Purchio A. F. Amplification and expression of heterologous oncostatin M in Chinese hamster ovary cells. DNA Cell Biol. 1992 Jul-Aug;11(6):453–459. doi: 10.1089/dna.1992.11.453. [DOI] [PubMed] [Google Scholar]
- Melnick J. L., Petrie B. L., Dreesman G. R., Burek J., McCollum C. H., DeBakey M. E. Cytomegalovirus antigen within human arterial smooth muscle cells. Lancet. 1983 Sep 17;2(8351):644–647. doi: 10.1016/s0140-6736(83)92529-1. [DOI] [PubMed] [Google Scholar]
- Miachon S., Biol M. C., Cier J. F., Chardonnet Y. Culture de cellules isolées de la fraction musculaire lisse de duodénum de rat. Cytobios. 1978;18(71-72):195–199. [PubMed] [Google Scholar]
- Miles S. A., Martínez-Maza O., Rezai A., Magpantay L., Kishimoto T., Nakamura S., Radka S. F., Linsley P. S. Oncostatin M as a potent mitogen for AIDS-Kaposi's sarcoma-derived cells. Science. 1992 Mar 13;255(5050):1432–1434. doi: 10.1126/science.1542793. [DOI] [PubMed] [Google Scholar]
- Molloy C. J., Bottaro D. P., Fleming T. P., Marshall M. S., Gibbs J. B., Aaronson S. A. PDGF induction of tyrosine phosphorylation of GTPase activating protein. Nature. 1989 Dec 7;342(6250):711–714. doi: 10.1038/342711a0. [DOI] [PubMed] [Google Scholar]
- Nair B. C., DeVico A. L., Nakamura S., Copeland T. D., Chen Y., Patel A., O'Neil T., Oroszlan S., Gallo R. C., Sarngadharan M. G. Identification of a major growth factor for AIDS-Kaposi's sarcoma cells as oncostatin M. Science. 1992 Mar 13;255(5050):1430–1432. doi: 10.1126/science.1542792. [DOI] [PubMed] [Google Scholar]
- Nishizuka Y. The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature. 1988 Aug 25;334(6184):661–665. doi: 10.1038/334661a0. [DOI] [PubMed] [Google Scholar]
- Qureshi S. A., Rim M., Bruder J., Kolch W., Rapp U., Sukhatme V. P., Foster D. A. An inhibitory mutant of c-Raf-1 blocks v-Src-induced activation of the Egr-1 promoter. J Biol Chem. 1991 Nov 5;266(31):20594–20597. [PubMed] [Google Scholar]
- Raines E. W., Dower S. K., Ross R. Interleukin-1 mitogenic activity for fibroblasts and smooth muscle cells is due to PDGF-AA. Science. 1989 Jan 20;243(4889):393–396. doi: 10.1126/science.2783498. [DOI] [PubMed] [Google Scholar]
- Richards C. D., Brown T. J., Shoyab M., Baumann H., Gauldie J. Recombinant oncostatin M stimulates the production of acute phase proteins in HepG2 cells and rat primary hepatocytes in vitro. J Immunol. 1992 Mar 15;148(6):1731–1736. [PubMed] [Google Scholar]
- Rose T. M., Bruce A. G. Oncostatin M is a member of a cytokine family that includes leukemia-inhibitory factor, granulocyte colony-stimulating factor, and interleukin 6. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8641–8645. doi: 10.1073/pnas.88.19.8641. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ross R., Masuda J., Raines E. W., Gown A. M., Katsuda S., Sasahara M., Malden L. T., Masuko H., Sato H. Localization of PDGF-B protein in macrophages in all phases of atherogenesis. Science. 1990 May 25;248(4958):1009–1012. doi: 10.1126/science.2343305. [DOI] [PubMed] [Google Scholar]
- Ross R., Raines E. W., Bowen-Pope D. F. The biology of platelet-derived growth factor. Cell. 1986 Jul 18;46(2):155–169. doi: 10.1016/0092-8674(86)90733-6. [DOI] [PubMed] [Google Scholar]
- Ross R. The pathogenesis of atherosclerosis--an update. N Engl J Med. 1986 Feb 20;314(8):488–500. doi: 10.1056/NEJM198602203140806. [DOI] [PubMed] [Google Scholar]
- Todderud G., Wahl M. I., Rhee S. G., Carpenter G. Stimulation of phospholipase C-gamma 1 membrane association by epidermal growth factor. Science. 1990 Jul 20;249(4966):296–298. doi: 10.1126/science.2374928. [DOI] [PubMed] [Google Scholar]
- Westermark B., Heldin C. H. Platelet-derived growth factor in autocrine transformation. Cancer Res. 1991 Oct 1;51(19):5087–5092. [PubMed] [Google Scholar]
- Williams L. T. Signal transduction by the platelet-derived growth factor receptor. Science. 1989 Mar 24;243(4898):1564–1570. doi: 10.1126/science.2538922. [DOI] [PubMed] [Google Scholar]
- Zarling J. M., Shoyab M., Marquardt H., Hanson M. B., Lioubin M. N., Todaro G. J. Oncostatin M: a growth regulator produced by differentiated histiocytic lymphoma cells. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9739–9743. doi: 10.1073/pnas.83.24.9739. [DOI] [PMC free article] [PubMed] [Google Scholar]