Control of smooth muscle cell growth by components of the extracellular matrix: autocrine role for thrombospondin
| Autor: | Paul Bornstein, Susan Coates Cook, Richard A. Majack |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1986 |
| Předmět: |
medicine.medical_treatment
Biology Muscle Smooth Vascular Extracellular matrix Epidermal growth factor medicine Animals Autocrine signalling Thrombospondins Growth Substances Cells Cultured Glycoproteins Thrombospondin Multidisciplinary Epidermal Growth Factor Cell growth Heparin Growth factor Cell Cycle Drug Synergism musculoskeletal system Growth Inhibitors Cell biology Extracellular Matrix Rats Biochemistry biology.protein cardiovascular system Platelet-derived growth factor receptor Research Article |
| Popis: | Addition of platelet-derived growth factor (PDGF) to growth-arrested cultured smooth muscle cells (SMC) induces the synthesis and secretion of thrombospondin (TS), a glycoprotein component of the SMC extracellular matrix in vitro. This induction occurs at PDGF concentrations that are suboptimal for a mitogenic response. In this study we examined the effect of TS on the proliferation of SMC, using a serum-free mitogenesis assay. Addition of either epidermal growth factor (EGF) or purified human platelet TS to quiescent rat vascular SMC did not substantially stimulate mitogenesis; the 30-hr nuclear labeling index increased from a mean of 7% in control cells to 20% for EGF-treated SMC and 17% for cells exposed to TS alone. However, TS and EGF acted synergistically to stimulate DNA synthesis by SMC, increasing the labeling index to 47%. The facilitative effect of TS on EGF-mediated mitogenesis was inhibited by heparin, a known inhibitor of SMC growth and migration that also blocks incorporation of TS into the SMC extracellular matrix. The effect was specific for EGF; TS did not augment the response of cells to insulin or insulin-like growth factor 1. These data establish a functional role for cell-derived TS and provide evidence for the presence of an autocrine, growth-supportive mechanism involving the extracellular matrix. In addition, our experiments support the existence of a novel, heparin-sensitive SMC mitogenic pathway and suggest a mechanism whereby heparin-like molecules may inhibit SMC proliferation. |
| Databáze: | OpenAIRE |
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