scholarly journals The Effect of Extracellular Matrix Proteins on Porcine Smooth Muscle Cell Insulin-like Growth Factor (IGF) Binding Protein-5 Synthesis and Responsiveness to IGF-I

1998 ◽  
Vol 273 (15) ◽  
pp. 8994-9000 ◽  
Author(s):  
Bo Zheng ◽  
Cumming Duan ◽  
David R. Clemmons
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein

scholarly journals Binding of Insulin-like Growth Factor (IGF)–Binding Protein-5 to Smooth-Muscle Cell Extracellular Matrix Is a Major Determinant of the Cellular Response to IGF-I

1998 ◽  
Vol 9 (9) ◽  
pp. 2383-2392 ◽  
Author(s):  
Alex Parker ◽  
Catherine Rees ◽  
Jane Clarke ◽  
Walker H. Busby ◽  
David R. Clemmons
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Cellular Response ◽  
Binding Protein ◽  
Important Variable ◽  
Insulin Like Growth Factor ◽  
Igf I

Insulin-like growth factor–binding protein-5 (IGFBP-5) has been shown to bind to fibroblast extracellular matrix (ECM). Extracellular matrix binding of IGFBP-5 leads to a decrease in its affinity for insulin-like growth factor-I (IGF-I), which allows IGF-I to better equilibrate with IGF receptors. When the amount of IGFBP-5 that is bound to ECM is increased by exogenous addition, IGF-I’s effect on fibroblast growth is enhanced. In this study we identified the specific basic residues in IGFBP-5 that mediate its binding to porcine smooth-muscle cell (pSMC) ECM. An IGFBP-5 mutant containing alterations of basic residues at positions 211, 214, 217, and 218 had the greatest reduction in ECM binding, although three other mutants, R214A, R207A/K211N, and K202A/R206N/R207A, also had major decreases. In contrast, three other mutants, R201A/K202N/R206N/R208A, and K217N/R218A and K211N, had only minimal reductions in ECM binding. This suggested that residues R207 and R214 were the most important for binding, whereas alterations in K211 and R218, which align near them, had minimal effects. To determine the effect of a reduction in ECM binding on the cellular replication response to IGF-I, pSMCs were transfected with the mutant cDNAs that encoded the forms of IGFBPs with the greatest changes in ECM binding. The ECM content of IGFBP-5 from cultures expressing the K211N, R214A, R217A/R218A, and K202A/R206N/R207A mutants was reduced by 79.6 and 71.7%, respectively, compared with cells expressing the wild-type protein. In contrast, abundance of the R201A/K202N/R206N/R208A mutant was reduced by only 14%. Cells expressing the two mutants with reduced ECM binding had decreased DNA synthesis responses to IGF-I, but the cells expressing the R201A/K202N/R206N/R208A mutant responded well to IGF-I. The findings suggest that specific basic amino acids at positions 207 and 214 mediate the binding of IGFBP-5 to pSMC/ECM. Smooth-muscle cells that constitutively express the mutants that bind weakly to ECM are less responsive to IGF-I, suggesting that ECM binding of IGFBP-5 is an important variable that determines cellular responsiveness.

scholarly journals Regulation of Vascular Smooth Muscle Cell Responses to Insulin-like Growth Factor (IGF)-I by Local IGF-binding Proteins

2003 ◽  
Vol 278 (44) ◽  
pp. 42886-42892 ◽  
Author(s):  
Tzefu Hsieh ◽  
Rebecca E. Gordon ◽  
David R. Clemmons ◽  
Walker H. Busby ◽  
Cunming Duan
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Igf Binding Proteins ◽  
Cell Responses ◽  
Igf I ◽  
Igf Binding

scholarly journals Hyperglycemia Alters the Responsiveness of Smooth Muscle Cells to Insulin-Like Growth Factor-I

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 2435-2443 ◽  
Author(s):  
Laura A. Maile ◽  
Byron E. Capps ◽  
Yan Ling ◽  
Gang Xi ◽  
David R. Clemmons
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Mapk Pathway ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Downstream Signaling ◽  
Igf I ◽  
Cell Migration And Proliferation ◽  
Stimulation Of ◽  
In Cells

IGF-I stimulation of smooth muscle cell (SMC) migration and proliferation requires αVβ3 ligand occupancy. We hypothesized that changes in the levels of extracellular matrix proteins induced by alterations in glucose concentrations may regulate the ability of SMCs to respond to IGF-I. IGF-I stimulated migration and proliferation of SMCs that had been maintained in 25 mm glucose containing media, but it had no stimulatory effect when tested using SMCs that had been grown in 5 mm glucose. IGF-I stimulated an increase in Shc phosphorylation and enhanced activation of the MAPK pathway in SMCs grown in 25 mm glucose, whereas in cells maintained in 5 mm glucose, IGF-I had no effect on Shc phosphorylation, and the MAPK response to IGF-I was markedly reduced. In cells grown in 25 mm glucose, the levels of αVβ3 ligands, e.g. osteopontin, vitronectin, and thrombospondin, were all significantly increased, compared with cells grown in 5 mm glucose. The addition of these αVβ3 ligands to SMCs grown in 5 mm glucose was sufficient to permit IGF-I-stimulated Shc phosphorylation and downstream signaling. Because we have shown previously that αVβ3 ligand occupancy is required for IGF-I-stimulated Shc phosphorylation and stimulation of SMC growth, our data are consistent with a model in which 25 mm glucose stimulates increases in the concentrations of these extracellular matrix proteins, thus enhancing αVβ3 ligand occupancy, which leads to increased Shc phosphorylation and enhanced cell migration and proliferation in response to IGF-I.

Sign in / Sign up

Export Citation Format

Share Document