Collagen synthesis in cultured aortic smooth muscle cells. Modulation by collagen lattice culture, transforming growth factor-beta 1, and epidermal growth factor.

We investigated the effects of transforming growth factor-beta 1 (TGF-beta 1) and epidermal growth factor (EGF) on the protein synthesis and production of collagen in cultured smooth muscle cells (SMCs) from the aortic media of pigs. SMCs were cultured as monolayers on plastic as well as in three-dimensional collagen lattices to gain some information about the influence of a preexisting collagenous matrix on the growth factor-induced effects. A 48-hour exposure of SMCs to TGF-beta 1 at concentrations of 5 ng/ml in the presence of 1% serum caused a marked enhancement of the production of collagen and noncollagen proteins. The rate of net collagen production by SMCs exposed to TGF-beta 1 was approximately threefold higher than that of control cells. Moreover, TGF-beta 1 specifically stimulated collagen synthesis, resulting in a greater proportion of collagen in total proteins synthesized compared with controls. The preexisting matrix of collagen lattices affects the response of SMCs to TGF-beta 1 and EGF. In monolayer cultures the collagen proportion increased twofold under the influence of TGF-beta 1, whereas in collagen lattices the specific stimulation of collagen synthesis was lower. We found that EGF enhanced TGF-beta 1-induced protein production in collagen lattices but not in monolayer cultures. In addition, the protein production by SMCs was influenced differently by EGF in these culture systems. Taken together, these data show a mutual influence of growth factors and extracellular matrix components on collagen production in SMCs, thus indicating that TGF-beta 1 may be an important pathophysiological regulator of collagen metabolism in the vessel wall.

[1]  B. Buchholz,et al.  Localization of cytoplasmic collagen mRNA in human aortic coarctation: mRNA enhancement in high blood pressure-induced intimal and medial thickening. , 1990, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[2]  H. Kresse,et al.  Influence of collagen lattice on the metabolism of small proteoglycan II by cultured fibroblasts. , 1990, The Biochemical journal.

[3]  H. Kresse,et al.  Deposition and ultrastructural organization of collagen and proteoglycans in the extracellular matrix of gel-cultured fibroblasts. , 1989, European journal of cell biology.

[4]  J. Engel.  EGF‐like domains in extracellular matrix proteins: Localized signals for growth and differentiation? , 1989, FEBS letters.

[5]  R. Page,et al.  Collagen synthesis by human fibroblasts. Regulation by transforming growth factor-beta in the presence of other inflammatory mediators. , 1989, The Biochemical journal.

[6]  H. Robenek,et al.  Mechanical confinement inhibits collagen synthesis in gel-cultured fibroblasts. , 1989, European journal of cell biology.

[7]  A. Rizzino.  Transforming growth factor-β: Multiple effects on cell differentiation and extracellular matrices , 1988 .

[8]  A. Mauviel,et al.  Transforming growth factor β stimulates collagen and glycosaminoglycan biosynthesis in cultured rabbit articular chondrocytes , 1988 .

[9]  M. Sporn,et al.  A nuclear factor 1 binding site mediates the transcriptional activation of a type I collagen promoter by transforming growth factor-β , 1988, Cell.

[10]  B. Nusgens,et al.  Modulation of cellular biosynthetic activity in the retracting collagen lattice. , 1987, European journal of cell biology.

[11]  J. Rosenbloom,et al.  Transforming growth factor beta (TGF beta) causes a persistent increase in steady-state amounts of type I and type III collagen and fibronectin mRNAs in normal human dermal fibroblasts. , 1987, The Biochemical journal.

[12]  M. Sporn,et al.  Some recent advances in the chemistry and biology of transforming growth factor-beta , 1987, The Journal of cell biology.

[13]  M. Sporn,et al.  Expression and secretion of type beta transforming growth factor by activated human macrophages. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[14]  W. Mckeehan,et al.  Transforming growth factor type beta specifically stimulates synthesis of proteoglycan in human adult arterial smooth muscle cells. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[15]  R. Mecham,et al.  Smooth muscle-mediated connective tissue remodeling in pulmonary hypertension. , 1987, Science.

[16]  H. Moses,et al.  Transforming growth factor-beta increases steady state levels of type I procollagen and fibronectin messenger RNAs posttranscriptionally in cultured human dermal fibroblasts. , 1987, The Journal of clinical investigation.

[17]  A. Fine,et al.  The effect of transforming growth factor-beta on cell proliferation and collagen formation by lung fibroblasts. , 1987, The Journal of biological chemistry.

[18]  E. Canalis,et al.  Transforming growth factor beta is a bifunctional regulator of replication and collagen synthesis in osteoblast-enriched cell cultures from fetal rat bone. , 1987, The Journal of biological chemistry.

[19]  P. Bornstein,et al.  Control of smooth muscle cell growth by components of the extracellular matrix: autocrine role for thrombospondin. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[20]  M. Sporn,et al.  Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[21]  M. Sporn,et al.  Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth , 1986, The Journal of experimental medicine.

[22]  M. Sporn,et al.  Type beta transforming growth factor in human platelets: release during platelet degranulation and action on vascular smooth muscle cells , 1986, The Journal of cell biology.

[23]  J. Massagué,et al.  Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. , 1986, The Journal of biological chemistry.

[24]  R. Ross.  The pathogenesis of atherosclerosis--an update. , 1986, The New England journal of medicine.

[25]  P. Bornstein,et al.  Platelet-derived growth factor and heparin-like glycosaminoglycans regulate thrombospondin synthesis and deposition in the matrix by smooth muscle cells , 1985, The Journal of cell biology.

[26]  V. Muzykantov,et al.  Distribution of type I, III, IV and V collagen in normal and atherosclerotic human arterial wall: immunomorphological characteristics. , 1985, Collagen and related research.

[27]  B. Nusgens,et al.  Collagen biosynthesis by cells in a tissue equivalent matrix in vitro. , 1984, Collagen and related research.

[28]  M. Sporn,et al.  Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. , 1983, The Journal of biological chemistry.

[29]  P. Bornstein,et al.  Thrombospondin: synthesis and secretion by cells in culture , 1982, The Journal of cell biology.

[30]  M. Sporn,et al.  New class of transforming growth factors potentiated by epidermal growth factor: isolation from non-neoplastic tissues. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[31]  R. Ross,et al.  Phenotype-dependent response of cultured aortic smooth muscle to serum mitogens , 1981, The Journal of cell biology.

[32]  G. Laurie,et al.  Biological activities of laminin , 1985, Journal of cellular biochemistry.

[33]  M. Barnes,et al.  Collagens in atherosclerosis. , 1985, Collagen and related research.