Abstract
Vascular smooth muscle cells (SMCs) are very quiescent in the mature vessel and exhibit a remarkable phenotype-dependent diversity in gene expression that may reflect the growth responsiveness of these cells under a variety of normal and pathological conditions. In this report, we describe the expression pattern of Oct-1, a member of a family of transcription factors involved in cell growth processes, in cultured and in in vivo SMCs. Oct-1 mRNA was undetectable in the contractile-state in vivo SMCs; was induced upon disruption of in vivo SMC-extracellular matrix interactions; and was constitutively expressed by cultured SMCs. Oct-1 transcripts were repressed when cultured SMCs were plated on Engelbreth-Holm-Swarm tumor-derived basement membranes (EHS-BM) but were rapidly induced after disruption of SMC-EHS-BM contacts; reexpression was regulated at the transcriptional level. To identify the EHS-BM component involved in the active repression of Oct-1 mRNA expression, SMCs were plated on laminin, type IV collagen, fibronectin, or perlecan matrices. Oct-1 mRNA levels were readily detectable when SMCs were cultured on matrices composed of laminin, type IV collagen, or fibronectin but were repressed when SMCs were cultured on perlecan matrices. Finally, the Oct-1-suppressing activity of EHS-BM was sensitive to heparinase digestion but not to chondroitinase ABC or hyaluronidase digestion, suggesting that the heparan sulfate side chains of perlecan play a biologically important role in negatively regulating the expression of Oct-1 transcripts.
Full text
PDF












Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adams J. C., Watt F. M. Regulation of development and differentiation by the extracellular matrix. Development. 1993 Apr;117(4):1183–1198. doi: 10.1242/dev.117.4.1183. [DOI] [PubMed] [Google Scholar]
- Assoian R. K., Sporn M. B. Type beta transforming growth factor in human platelets: release during platelet degranulation and action on vascular smooth muscle cells. J Cell Biol. 1986 Apr;102(4):1217–1223. doi: 10.1083/jcb.102.4.1217. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Au Y. P., Kenagy R. D., Clowes M. M., Clowes A. W. Mechanisms of inhibition by heparin of vascular smooth muscle cell proliferation and migration. Haemostasis. 1993 Mar;23 (Suppl 1):177–182. doi: 10.1159/000216926. [DOI] [PubMed] [Google Scholar]
- Benitz W. E., Kelley R. T., Anderson C. M., Lorant D. E., Bernfield M. Endothelial heparan sulfate proteoglycan. I. Inhibitory effects on smooth muscle cell proliferation. Am J Respir Cell Mol Biol. 1990 Jan;2(1):13–24. doi: 10.1165/ajrcmb/2.1.13. [DOI] [PubMed] [Google Scholar]
- Bernards R., Shackleford G. M., Schackleford G. M., Gerber M. R., Horowitz J. M., Friend S. H., Schartl M., Bogenmann E., Rapaport J. M., McGee T. Structure and expression of the murine retinoblastoma gene and characterization of its encoded protein. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6474–6478. doi: 10.1073/pnas.86.17.6474. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bernfield M., Hinkes M. T., Gallo R. L. Developmental expression of the syndecans: possible function and regulation. Dev Suppl. 1993:205–212. [PubMed] [Google Scholar]
- Campbell J. H., Rennick R. E., Kalevitch S. G., Campbell G. R. Heparan sulfate-degrading enzymes induce modulation of smooth muscle phenotype. Exp Cell Res. 1992 May;200(1):156–167. doi: 10.1016/s0014-4827(05)80084-9. [DOI] [PubMed] [Google Scholar]
- Castellot J. J., Jr, Addonizio M. L., Rosenberg R., Karnovsky M. J. Cultured endothelial cells produce a heparinlike inhibitor of smooth muscle cell growth. J Cell Biol. 1981 Aug;90(2):372–379. doi: 10.1083/jcb.90.2.372. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chakravarti S., Horchar T., Jefferson B., Laurie G. W., Hassell J. R. Recombinant domain III of perlecan promotes cell attachment through its RGDS sequence. J Biol Chem. 1995 Jan 6;270(1):404–409. doi: 10.1074/jbc.270.1.404. [DOI] [PubMed] [Google Scholar]
- Chamley-Campbell J. H., Campbell G. R., Ross R. Phenotype-dependent response of cultured aortic smooth muscle to serum mitogens. J Cell Biol. 1981 May;89(2):379–383. doi: 10.1083/jcb.89.2.379. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cizmeci-Smith G., Asundi V., Stahl R. C., Teichman L. J., Chernousov M., Cowan K., Carey D. J. Regulated expression of syndecan in vascular smooth muscle cells and cloning of rat syndecan core protein cDNA. J Biol Chem. 1992 Aug 5;267(22):15729–15736. [PubMed] [Google Scholar]
- Clowes A. W., Karnowsky M. J. Suppression by heparin of smooth muscle cell proliferation in injured arteries. Nature. 1977 Feb 17;265(5595):625–626. doi: 10.1038/265625a0. [DOI] [PubMed] [Google Scholar]
- Cook C. L., Weiser M. C., Schwartz P. E., Jones C. L., Majack R. A. Developmentally timed expression of an embryonic growth phenotype in vascular smooth muscle cells. Circ Res. 1994 Feb;74(2):189–196. doi: 10.1161/01.res.74.2.189. [DOI] [PubMed] [Google Scholar]
- Couchman J. R. Heterogeneous distribution of a basement membrane heparan sulfate proteoglycan in rat tissues. J Cell Biol. 1987 Oct;105(4):1901–1916. doi: 10.1083/jcb.105.4.1901. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ferns G. A., Raines E. W., Sprugel K. H., Motani A. S., Reidy M. A., Ross R. Inhibition of neointimal smooth muscle accumulation after angioplasty by an antibody to PDGF. Science. 1991 Sep 6;253(5024):1129–1132. doi: 10.1126/science.1653454. [DOI] [PubMed] [Google Scholar]
- Fletcher C., Heintz N., Roeder R. G. Purification and characterization of OTF-1, a transcription factor regulating cell cycle expression of a human histone H2b gene. Cell. 1987 Dec 4;51(5):773–781. doi: 10.1016/0092-8674(87)90100-0. [DOI] [PubMed] [Google Scholar]
- Frid M. G., Moiseeva E. P., Stenmark K. R. Multiple phenotypically distinct smooth muscle cell populations exist in the adult and developing bovine pulmonary arterial media in vivo. Circ Res. 1994 Oct;75(4):669–681. doi: 10.1161/01.res.75.4.669. [DOI] [PubMed] [Google Scholar]
- Fritze L. M., Reilly C. F., Rosenberg R. D. An antiproliferative heparan sulfate species produced by postconfluent smooth muscle cells. J Cell Biol. 1985 Apr;100(4):1041–1049. doi: 10.1083/jcb.100.4.1041. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Galis Z. S., Muszynski M., Sukhova G. K., Simon-Morrissey E., Unemori E. N., Lark M. W., Amento E., Libby P. Cytokine-stimulated human vascular smooth muscle cells synthesize a complement of enzymes required for extracellular matrix digestion. Circ Res. 1994 Jul;75(1):181–189. doi: 10.1161/01.res.75.1.181. [DOI] [PubMed] [Google Scholar]
- Glukhova M. A., Frid M. G., Koteliansky V. E. Developmental changes in expression of contractile and cytoskeletal proteins in human aortic smooth muscle. J Biol Chem. 1990 Aug 5;265(22):13042–13046. [PubMed] [Google Scholar]
- Hassell J. R., Robey P. G., Barrach H. J., Wilczek J., Rennard S. I., Martin G. R. Isolation of a heparan sulfate-containing proteoglycan from basement membrane. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4494–4498. doi: 10.1073/pnas.77.8.4494. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hayashi K., Madri J. A., Yurchenco P. D. Endothelial cells interact with the core protein of basement membrane perlecan through beta 1 and beta 3 integrins: an adhesion modulated by glycosaminoglycan. J Cell Biol. 1992 Nov;119(4):945–959. doi: 10.1083/jcb.119.4.945. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hedin U., Bottger B. A., Forsberg E., Johansson S., Thyberg J. Diverse effects of fibronectin and laminin on phenotypic properties of cultured arterial smooth muscle cells. J Cell Biol. 1988 Jul;107(1):307–319. doi: 10.1083/jcb.107.1.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Iozzo R. V., Cohen I. R., Grässel S., Murdoch A. D. The biology of perlecan: the multifaceted heparan sulphate proteoglycan of basement membranes and pericellular matrices. Biochem J. 1994 Sep 15;302(Pt 3):625–639. doi: 10.1042/bj3020625. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Järveläinen H. T., Kinsella M. G., Wight T. N., Sandell L. J. Differential expression of small chondroitin/dermatan sulfate proteoglycans, PG-I/biglycan and PG-II/decorin, by vascular smooth muscle and endothelial cells in culture. J Biol Chem. 1991 Dec 5;266(34):23274–23281. [PubMed] [Google Scholar]
- Kleinman H. K., McGarvey M. L., Hassell J. R., Star V. L., Cannon F. B., Laurie G. W., Martin G. R. Basement membrane complexes with biological activity. Biochemistry. 1986 Jan 28;25(2):312–318. doi: 10.1021/bi00350a005. [DOI] [PubMed] [Google Scholar]
- Kohler T. R., Jawien A. Flow affects development of intimal hyperplasia after arterial injury in rats. Arterioscler Thromb. 1992 Aug;12(8):963–971. doi: 10.1161/01.atv.12.8.963. [DOI] [PubMed] [Google Scholar]
- LaBella F., Sive H. L., Roeder R. G., Heintz N. Cell-cycle regulation of a human histone H2b gene is mediated by the H2b subtype-specific consensus element. Genes Dev. 1988 Jan;2(1):32–39. doi: 10.1101/gad.2.1.32. [DOI] [PubMed] [Google Scholar]
- Lakin N. D., Palmer R., Lillycrop K. A., Howard M. K., Burke L. C., Thomas N. S., Latchman D. S. Down regulation of the octamer binding protein Oct-1 during growth arrest and differentiation of a neuronal cell line. Brain Res Mol Brain Res. 1995 Jan;28(1):47–54. doi: 10.1016/0169-328x(94)00183-f. [DOI] [PubMed] [Google Scholar]
- Li X., Tsai P., Wieder E. D., Kribben A., Van Putten V., Schrier R. W., Nemenoff R. A. Vascular smooth muscle cells grown on Matrigel. A model of the contractile phenotype with decreased activation of mitogen-activated protein kinase. J Biol Chem. 1994 Jul 29;269(30):19653–19658. [PubMed] [Google Scholar]
- Lin C. Q., Bissell M. J. Multi-faceted regulation of cell differentiation by extracellular matrix. FASEB J. 1993 Jun;7(9):737–743. doi: 10.1096/fasebj.7.9.8330681. [DOI] [PubMed] [Google Scholar]
- Lindner V., Majack R. A., Reidy M. A. Basic fibroblast growth factor stimulates endothelial regrowth and proliferation in denuded arteries. J Clin Invest. 1990 Jun;85(6):2004–2008. doi: 10.1172/JCI114665. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Majack R. A., Bornstein P. Heparin and related glycosaminoglycans modulate the secretory phenotype of vascular smooth muscle cells. J Cell Biol. 1984 Nov;99(5):1688–1695. doi: 10.1083/jcb.99.5.1688. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Majack R. A., Clowes A. W. Inhibition of vascular smooth muscle cell migration by heparin-like glycosaminoglycans. J Cell Physiol. 1984 Mar;118(3):253–256. doi: 10.1002/jcp.1041180306. [DOI] [PubMed] [Google Scholar]
- Majack R. A., Cook S. C., Bornstein P. Platelet-derived growth factor and heparin-like glycosaminoglycans regulate thrombospondin synthesis and deposition in the matrix by smooth muscle cells. J Cell Biol. 1985 Sep;101(3):1059–1070. doi: 10.1083/jcb.101.3.1059. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Majesky M. W., Giachelli C. M., Reidy M. A., Schwartz S. M. Rat carotid neointimal smooth muscle cells reexpress a developmentally regulated mRNA phenotype during repair of arterial injury. Circ Res. 1992 Oct;71(4):759–768. doi: 10.1161/01.res.71.4.759. [DOI] [PubMed] [Google Scholar]
- Marcum J. A., Rosenberg R. D. Anticoagulantly active heparin-like molecules from vascular tissue. Biochemistry. 1984 Apr 10;23(8):1730–1737. doi: 10.1021/bi00303a023. [DOI] [PubMed] [Google Scholar]
- Mosse P. R., Campbell G. R., Wang Z. L., Campbell J. H. Smooth muscle phenotypic expression in human carotid arteries. I. Comparison of cells from diffuse intimal thickenings adjacent to atheromatous plaques with those of the media. Lab Invest. 1985 Nov;53(5):556–562. [PubMed] [Google Scholar]
- Murdoch A. D., Liu B., Schwarting R., Tuan R. S., Iozzo R. V. Widespread expression of perlecan proteoglycan in basement membranes and extracellular matrices of human tissues as detected by a novel monoclonal antibody against domain III and by in situ hybridization. J Histochem Cytochem. 1994 Feb;42(2):239–249. doi: 10.1177/42.2.7507142. [DOI] [PubMed] [Google Scholar]
- Noonan D. M., Fulle A., Valente P., Cai S., Horigan E., Sasaki M., Yamada Y., Hassell J. R. The complete sequence of perlecan, a basement membrane heparan sulfate proteoglycan, reveals extensive similarity with laminin A chain, low density lipoprotein-receptor, and the neural cell adhesion molecule. J Biol Chem. 1991 Dec 5;266(34):22939–22947. [PubMed] [Google Scholar]
- Noonan D. M., Hassell J. R. Perlecan, the large low-density proteoglycan of basement membranes: structure and variant forms. Kidney Int. 1993 Jan;43(1):53–60. doi: 10.1038/ki.1993.10. [DOI] [PubMed] [Google Scholar]
- Ottlinger M. E., Pukac L. A., Karnovsky M. J. Heparin inhibits mitogen-activated protein kinase activation in intact rat vascular smooth muscle cells. J Biol Chem. 1993 Sep 15;268(26):19173–19176. [PubMed] [Google Scholar]
- Owens G. K. Regulation of differentiation of vascular smooth muscle cells. Physiol Rev. 1995 Jul;75(3):487–517. doi: 10.1152/physrev.1995.75.3.487. [DOI] [PubMed] [Google Scholar]
- Pukac L. A., Ottlinger M. E., Karnovsky M. J. Heparin suppresses specific second messenger pathways for protooncogene expression in rat vascular smooth muscle cells. J Biol Chem. 1992 Feb 25;267(6):3707–3711. [PubMed] [Google Scholar]
- Rosenfeld M. G. POU-domain transcription factors: pou-er-ful developmental regulators. Genes Dev. 1991 Jun;5(6):897–907. doi: 10.1101/gad.5.6.897. [DOI] [PubMed] [Google Scholar]
- Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993 Apr 29;362(6423):801–809. doi: 10.1038/362801a0. [DOI] [PubMed] [Google Scholar]
- Ruvkun G., Finney M. Regulation of transcription and cell identity by POU domain proteins. Cell. 1991 Feb 8;64(3):475–478. doi: 10.1016/0092-8674(91)90227-p. [DOI] [PubMed] [Google Scholar]
- Sage E. H., Bornstein P. Extracellular proteins that modulate cell-matrix interactions. SPARC, tenascin, and thrombospondin. J Biol Chem. 1991 Aug 15;266(23):14831–14834. [PubMed] [Google Scholar]
- Schmidhauser C., Casperson G. F., Myers C. A., Sanzo K. T., Bolten S., Bissell M. J. A novel transcriptional enhancer is involved in the prolactin- and extracellular matrix-dependent regulation of beta-casein gene expression. Mol Biol Cell. 1992 Jun;3(6):699–709. doi: 10.1091/mbc.3.6.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz S. M., deBlois D., O'Brien E. R. The intima. Soil for atherosclerosis and restenosis. Circ Res. 1995 Sep;77(3):445–465. doi: 10.1161/01.res.77.3.445. [DOI] [PubMed] [Google Scholar]
- Schöler H. R. Octamania: the POU factors in murine development. Trends Genet. 1991 Oct;7(10):323–329. doi: 10.1016/0168-9525(91)90422-m. [DOI] [PubMed] [Google Scholar]
- Simons M., Leclerc G., Safian R. D., Isner J. M., Weir L., Baim D. S. Relation between activated smooth-muscle cells in coronary-artery lesions and restenosis after atherectomy. N Engl J Med. 1993 Mar 4;328(9):608–613. doi: 10.1056/NEJM199303043280903. [DOI] [PubMed] [Google Scholar]
- Snow A. D., Bolender R. P., Wight T. N., Clowes A. W. Heparin modulates the composition of the extracellular matrix domain surrounding arterial smooth muscle cells. Am J Pathol. 1990 Aug;137(2):313–330. [PMC free article] [PubMed] [Google Scholar]
- Soussi T., Caron de Fromentel C., Breugnot C., May E. Nucleotide sequence of a cDNA encoding the rat p53 nuclear oncoprotein. Nucleic Acids Res. 1988 Dec 9;16(23):11384–11384. doi: 10.1093/nar/16.23.11384. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stadler E., Campbell J. H., Campbell G. R. Do cultured vascular smooth muscle cells resemble those of the artery wall? If not, why not? J Cardiovasc Pharmacol. 1989;14 (Suppl 6):S1–S8. [PubMed] [Google Scholar]
- Streuli C. H., Schmidhauser C., Bailey N., Yurchenco P., Skubitz A. P., Roskelley C., Bissell M. J. Laminin mediates tissue-specific gene expression in mammary epithelia. J Cell Biol. 1995 May;129(3):591–603. doi: 10.1083/jcb.129.3.591. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sturm R. A., Das G., Herr W. The ubiquitous octamer-binding protein Oct-1 contains a POU domain with a homeo box subdomain. Genes Dev. 1988 Dec;2(12A):1582–1599. doi: 10.1101/gad.2.12a.1582. [DOI] [PubMed] [Google Scholar]
- Thyberg J. Differentiated properties and proliferation of arterial smooth muscle cells in culture. Int Rev Cytol. 1996;169:183–265. doi: 10.1016/s0074-7696(08)61987-7. [DOI] [PubMed] [Google Scholar]
- Thyberg J., Hultgårdh-Nilsson A. Fibronectin and the basement membrane components laminin and collagen type IV influence the phenotypic properties of subcultured rat aortic smooth muscle cells differently. Cell Tissue Res. 1994 May;276(2):263–271. doi: 10.1007/BF00306112. [DOI] [PubMed] [Google Scholar]
- Topouzis S., Majesky M. W. Smooth muscle lineage diversity in the chick embryo. Two types of aortic smooth muscle cell differ in growth and receptor-mediated transcriptional responses to transforming growth factor-beta. Dev Biol. 1996 Sep 15;178(2):430–445. doi: 10.1006/dbio.1996.0229. [DOI] [PubMed] [Google Scholar]
- Tso J. Y., Sun X. H., Kao T. H., Reece K. S., Wu R. Isolation and characterization of rat and human glyceraldehyde-3-phosphate dehydrogenase cDNAs: genomic complexity and molecular evolution of the gene. Nucleic Acids Res. 1985 Apr 11;13(7):2485–2502. doi: 10.1093/nar/13.7.2485. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weiser M. C., Belknap J. K., Grieshaber S. S., Kinsella M. G., Majack R. A. Developmental regulation of perlecan gene expression in aortic smooth muscle cells. Matrix Biol. 1996 Nov;15(5):331–340. doi: 10.1016/s0945-053x(96)90136-5. [DOI] [PubMed] [Google Scholar]
- Weiser M. C., Majack R. A., Tucker A., Orton E. C. Static tension is associated with increased smooth muscle cell DNA synthesis in rat pulmonary arteries. Am J Physiol. 1995 Mar;268(3 Pt 2):H1133–H1138. doi: 10.1152/ajpheart.1995.268.3.H1133. [DOI] [PubMed] [Google Scholar]
- Zerivitz K., Akusjärvi G. An improved nuclear extract preparation method. Gene Anal Tech. 1989 Sep-Oct;6(5):101–109. doi: 10.1016/0735-0651(89)90016-2. [DOI] [PubMed] [Google Scholar]











