Transition of Smooth Muscle Cells from the Quiescent to the Proliferative Form
Smooth muscle cells (SMCs) of the normal arterial wall are anchored on the surrounding matrix comprising collagen fibers and the concentric elastic lamellae. The contractility together with the elastic properties of the concentric elastic lamellae form a finely adjustable mechanochemical system regulating the tension of the arterial wall. We have isolated an inducible adhesive protein, elastonectin. which mediates the interaction between the elastic fibers and the SMC membrane. The biosynthesis of elastonectin could be induced by adding elastic fibers or soluble elastin peptides to the culture medium of porcine aorta SMCs or human skin fibroblasts. Cycloheximide inhibits this process, suggesting that the elastonectin-mediated adhesion of cells to elastic fibers necessitates active protein synthesis. Trypsin or elastase but not collagenase can detach the cell-adhering elastin fibers. The biosynthesis of elastonectin was demonstrated by inducing its synthesis with κ-elastin added to the cell cultures in the presence of [35S]methionine. The protein could be eluted from the elastic fibers with 4 M guanidine-0.1 M DTT after repeated washings with buffers and 1 M urea. The eluate exhibited a major band on SDS-PAGE at 120 kDa that increased in intensity in the induced cultures. This protein, elastonectin, together with other structural glycoproteins such as fibronectin, plays a role in the maintainance of the SMCs in their matrix-bound form.
The biosynthesis of the membrane-bound elastase-type serine protease was shown to increase with increasing number of cell population doublings (NPD), thus imitating the previously demonstrated (in vivo) age-dependent increase of elastase-type protease activity of human aortas. When LDL was added to the culture, the biosynthesis of the enzyme was significantly increased; HDL had no such effect. Since such enzymes can detach the cells from their matrix-fixed sites, the age-dependent increase of the SMC membrane elastase may well be involved in the phenotypic modulation of these cells. The elastin peptides liberated during their hydrolytic action exert a chemotactic effect on SMCs, increasing their migration towards the degraded elastic lamellae. Elastin peptides at low concentration activate the biosynthetic activity of SMCs. It appears, therefore, that the alternative synthesis of elastonectin and membrane-bound elastase of SMCs plays an important role in the modulation of their phenotypic behavior especially in the transition from sessile and contractile to the mobile and biosynthetic states. These processes are believed to play a crucial role in the development of the atherosclerotic lesions.
KeywordsSmooth Muscle Cell Elastic Fiber Human Skin Fibroblast Aorta Smooth Muscle Cell Elastase Activity
Unable to display preview. Download preview PDF.
- Garrone, R., Robert, L., Pavans de Ceccatty, M., and Vacelet, J., 1971, ultrastructure des filaments de éponge Ircinia variabilis, J. Microsc. 11:60–61.Google Scholar
- Hornebeck, W., and Robert, L., 1977, Elastase-like enzymes in aortas and human breast carcinomas: Quantitative variations with age and pathology, in: Elastin and Elastic Tissue (L. B. Sandberg, W. R. Gray, and C. Franzblau, eds.), Plenum Press, New York, pp. 145–164.Google Scholar
- Hornebeck, W., and Robert, L., 1986, Interactions between elastic fibers and cells, in: Frontiers of Matrix Biology ,Vol. 11,(J. Labat Robert, R. Timpl, and L. Robert, eds.), S. Karger, Basel, pp. 58–77.Google Scholar
- Hornebeck, W., Bréchemier, D., Soleilhac, J. P., Bourdillon, M. C., and Robert, L., 1985a, Studies on rat aorta smooth muscle cells elastase activity, in: Extracellular Matrix: Structure and Function, Vol. 25 (A. H. Reddi, ed.), Alan R. Liss, New York, pp. 269–282.Google Scholar
- Robert, L., and Robert, A. M., 1980, Elastin, elastase and arteriosclerosis, in: Frontiers of Matrix Biology ,Vol. 8 (A. M. Robert and L. Robert, eds.), S. Karger, Basel, pp. 130–173.Google Scholar
- Robert, L., Hornebeck, W., and Robert, A. M., 1983, Role of connective tissue in the arterio-athero-sclerosis process. Interest of a cell-matrix directed pharmacology, in: Atherosclerosis ,Vol. 6 (G. F. Schettler, A. M. Gotto, G. Middelhoff, A. J. R. Habenicht, and K. R. Jurutka, eds.), Springer-Verlag, Berlin, pp. 370–380.Google Scholar