Platelet-derived growth factor and heparin-like glycosaminoglycans regulate thrombospondin synthesis and deposition in the matrix by smooth muscle cells.

Majack, Richard A.; Cook, Susan Coates; Börnstein, Paul

doi:10.1083/jcb.101.3.1059

Cited by 228 publications

(164 citation statements)

References 75 publications

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“…Perlecan is widely expressed in the basement membranes of adult tissues and in all vascular structures (Couchman, 1987;Murdoch et al, 1994) and has been directly implicated as a potent endothelial cell-derived inhibitor of SMC replication (Benitz et al, 1990). Our data indicate that at least some of the gene-regulating activity of perlecan resides in its heparan sulfate side chains, consistent with a large body of evidence implicating heparin-like molecules in the regulation of various SMC functions (Clowes and Karnovsky, 1977;Castellot et al, 1981;Majack and Bornstein, 1984;Majack and Clowes, 1984;Marcum and Rosenberg, 1984;Majack et al, 1985;Fritze et al, 1985;Benitz et al, 1990;Campbell et al, 1992;Pukac et al, 1992;Au et al, 1993).…”

Section: Role Of Basement Membrane Components Insupporting

confidence: 70%

Perlecan regulates Oct-1 gene expression in vascular smooth muscle cells.

Weiser

Grieshaber

Schwartz

et al. 1997

MBoC

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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.

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Section: Role Of Basement Membrane Components Insupporting

confidence: 70%

Perlecan regulates Oct-1 gene expression in vascular smooth muscle cells.

Weiser

Grieshaber

Schwartz

et al. 1997

MBoC

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“…Both platelet-derived growth factor (PDGF) and transforming growth factor-␤ (TGF-␤) have been shown to induce TSP-1 secretion from vascular smooth muscle cells (VSMCs). 11,12 TSP-1 mRNA levels have been shown to be similarly regulated. Basic fibroblast growth factor upregulates TSP-1 mRNA in 3T3 cells, 13 and PDGF induces upregulation in a manner similar to that of c-myc and c-fos, with TSP-1 being classified as an immediate early response gene.…”

mentioning

confidence: 84%

Phosphatidylinositol 3-Kinase and Focal Adhesion Kinase Are Early Signals in the Growth Factor–Like Responses to Thrombospondin-1 Seen in Human Vascular Smooth Muscle

Lymn

Rao

Clunn

et al. 1999

ATVB

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Abstract-Thrombospondin-1 (TSP-1) is a matricellular protein that is expressed in negligible amounts in normal blood vessels but is markedly upregulated in vascular injury. Although TSP-1 can act as a pleiotropic regulator for human vascular smooth muscle cells (HVSMCs), the intracellular signaling pathways stimulated by this protein remain obscure. In cultured HVSMCs derived from saphenous vein, TSP-1 induces tyrosine phosphorylation of a number of cellular proteins, with a complex temporal pattern of activation. Immunoprecipitation techniques have identified the early tyrosine-phosphorylated signals as being the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI 3-K) and focal adhesion kinase (FAK). Tyrosine phosphorylation of the p85 subunit of PI 3-K showed a biphasic response to TSP-1 stimulation, which corresponded to a biphasic activation of the lipid kinase. Treatment with both wortmannin and LY294002 inhibited PI 3-K activity of HVSMCs but did not affect tyrosine phosphorylation of the p85 regulatory subunit. TSP-1-stimulated FAK phosphorylation, however, was substantially reduced by these inhibitors, as was the TSP-1-induced chemotaxis of these cells. These results suggest that activation of PI 3-K is an early signal induced by TSP-1 and is critical for chemotaxis. Activation of this kinase precedes and may occur upstream from FAK phosphorylation, although the nature of the interaction between these 2 enzymes remains obscure. Key Words: thrombospondin-1 Ⅲ focal adhesion kinase Ⅲ phosphatidylinositol 3-kinase Ⅲ human vascular smooth muscle T hrombospondin-1 (TSP-1), a large, homotrimeric glycoprotein, is a member of the TSP family of matricellular proteins. This family currently consists of 5 isoforms: TSP-1 through TSP-4 and TSP-5/cartilage oligomeric matrix protein, 1 which, although implicated in a wide variety of biological processes, 2 show differential tissue expression both temporally and spatially. 3,4 TSP-1 was originally described as a product of platelet ␣-granules 5 but has since been shown to be synthesized by a number of different cell types, including vascular endothelial and smooth muscle cells. 6,7 TSP-1 is present in negligible amounts in normal human blood vessels, but the expression of this protein is markedly upregulated in injured and diseased vasculature, 8 -10 suggesting a possible role for TSP-1 in the abnormal cellular response to vascular injury.Literature evidence would suggest that TSP-1 levels are regulated by growth factors. Both platelet-derived growth factor (PDGF) and transforming growth factor-␤ (TGF-␤) have been shown to induce TSP-1 secretion from vascular smooth muscle cells (VSMCs). 11,12 TSP-1 mRNA levels have been shown to be similarly regulated. Basic fibroblast growth factor upregulates TSP-1 mRNA in 3T3 cells, 13 and PDGF induces upregulation in a manner similar to that of c-myc and c-fos, with TSP-1 being classified as an immediate early response gene. 14 These data, in conjunction with the role of TSP-1 in potentiating the chemotactic response of VS...

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“…Earlier studies have demonstrated an increased TSP-1 expression in response to serum, PDGF, and TGF-␤ in rat SMCs. [31][32][33][34] These differences might be due to several factors. (1) It is known that at least mouse and human TSP-1 promotor regions differ in their transcription factor binding sites and their serum responsive elements.…”

Section: Discussionmentioning

confidence: 99%

“…(1) It is known that at least mouse and human TSP-1 promotor regions differ in their transcription factor binding sites and their serum responsive elements. 16,35 (2) In the work by Majack et al, [31][32][33] mostly PDGF and TGF-␤ isolated from platelets were used, which might contain a mixture of different growth factor isoforms (eg, PDGF-AA, -AB, and -BB) and might also be contaminated by other growth factors (purity was Ͼ95%). In the study by Hugo et al, 34 the source of PDGF-BB was not mentioned.…”

Section: Discussionmentioning

confidence: 99%