Growth Stimulation of Human Skin Fibroblasts by Elastin-Derived Peptides

Kamoun, Aurélie; Landeau, J M; Godeau, Gaston; Wallach, Jean; Duchesnay, Arlette; Pellat, B.; Hornebeck, William

doi:10.3109/15419069509081013

Cited by 92 publications

(63 citation statements)

References 20 publications

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“…Moreover, immunoprecipitation with antiphosphotyrosine antibody followed by Western blotting with the antibody recognizing 15-kDa LC3 microtubule-associated protein 1, showed significant up-regulation of this protein (data not shown), which is also known as a factor facilitating translation of fibronectin mRNA (54). DISCUSSION Results presented in this report showed that, similar to other cell types (15)(16)(17)(18)(19), cultured SMC isolated from porcine coronary FIG. 5.…”

Section: Resultssupporting

confidence: 58%

“…It has also been suggested that local accumulation of non-assembled tropoelastin and small elastin-derived peptides may constitute an important factor in the activation of the normally quiescent medial SMC 1 into the proliferative and migratory phenotype, which participates in the formation of the occlusive neointima in vascular diseases (2,3,(11)(12)(13)(14)(15). Results of in vitro studies have also established that elastinderived peptides can stimulate proliferation of human skin fibroblasts (16), lymphoblasts (17), and several types of cancer cells (18,19) as well as cellular chemotaxis and chemokinesis (18, 20 -24). Elastin does not contain the RGD sequence and does not interact with cell surface integrins.…”

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confidence: 90%

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Signaling Pathways Transduced through the Elastin Receptor Facilitate Proliferation of Arterial Smooth Muscle Cells

Mochizuki

Brassart

Hinek

2002

Journal of Biological Chemistry

219

148

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In this report we demonstrate that soluble peptides, elastin degradation products stimulate proliferation of arterial smooth muscle cells. We show that these effects are due to generation of intracellular signals transduced through the cell surface elastin receptor, which consists of peripheral 67-kDa elastin-binding protein (EBP) (spliced variant of ␤-galactosidase), immobilized to the transmembrane sialidase and the protective protein. We found that elastin receptor-transduced signaling triggers activation of G proteins, opening of L-type calcium channels, and a sequential activation of tyrosine kinases: FAK, c-Src, platelet-derived growth factorreceptor kinase and then Ras-Raf-MEK1/2-ERK1/2 phosphorylation cascade. This, in turn, causes an increase in expression of cyclins and cyclin-dependent kinases, and a consequent increase in cellular proliferation. The EBP-transduced signals also induce tyrosine kinase-dependent phosphorylation of ␤-tubulin, LC3, microtubule-associated protein 1, and ␣-actin and troponin-T, which could be linked to reorganization of cytoskeleton. We have also disclosed that induction of these signals can be abolished by anti-EBP antibody or by galactosugars, which cause shedding of EBP from the cell surface. Moreover, elastin-derived peptides did not induce proliferation of EBP-deficient cells derived from patients bearing a nonsense mutation of the ␤-galactosidase gene or sialidase-deficient cells from patients with congenital sialidosis.It has been well established that formation of neointima in vascular diseases is associated with impaired assembly of tropoelastin into insoluble elastin (1-6) and with extensive degradation of the elastin-rich extracellular matrix by numerous proteinases leaking from the serum and secreted from the infiltrating platelets, leukocytes, and activated vascular cells (7-10). It has also been suggested that local accumulation of non-assembled tropoelastin and small elastin-derived peptides may constitute an important factor in the activation of the normally quiescent medial SMC 1 into the proliferative and migratory phenotype, which participates in the formation of the occlusive neointima in vascular diseases (2,3,(11)(12)(13)(14)(15) Elastin does not contain the RGD sequence and does not interact with cell surface integrins. Our previous studies demonstrated that numerous cell types, including vascular myocytes, express the cell surface elastin receptor complex, which consists of three subunits (25,26), and that the average cell contains ϳ2 ϫ 10 6 elastin binding sites with the binding affinity (K d ) of 8 nM (27). We found that two of those subunits (55-and 61-kDa) are anchored to the plasma membrane, whereas the third, a peripheral 67-kDa protein, actually binds elastin (25). This major functional component of the receptor complex was named the elastin binding protein (EBP). The repeat hexapeptide in tropoelastin, VGVAPG, has been identified as a chief ligand for high affinity binding to this cell surface receptor (25-27). It has been later established t...

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Section: Resultssupporting

confidence: 58%

mentioning

confidence: 90%

Signaling Pathways Transduced through the Elastin Receptor Facilitate Proliferation of Arterial Smooth Muscle Cells

Mochizuki

Brassart

Hinek

2002

Journal of Biological Chemistry

219

148

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“…Thus, any sign of its degradation can represent a vital signal for organisms to initiate effective repair processes. Overall, those peptides were reported to display a wide range of biological activities, influencing cell migration (Senior et al, 1980;Hinek et al, 1992), differentiation (Grant et al, 1989), proliferation and chemotaxis (Kamoun et al, 1995;Ghuysen et al, 1992), tumor progression (Lapis and Timar, 2002;Timar et al, 1991;Huet et al, 2002;Ntayi et al, 2004), aneurysm formation and atherogenesis (Nackman et al, 1997;Hance et al, 2002;Robert, 1996). With regard to tumor invasion, soluble peptides from alkaline (κ-elastin) or elastase hydrolysis of insoluble elastin, as well as tropoelastin were shown to increase MMP-2 and MMP-3 production by human skin fibroblasts Huet et al, 2001); similarly, κ-elastin stimulated MMP-2, MT1-MMP and TIMP-2 expression in human HT-1080 fibrosarcoma cell lines and, as a consequence, could promote the invasive metastatic ability of tumor cells (Huet et al, 2002;Brassart et al, 1998).…”

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confidence: 99%

Elastin-derived peptides enhance angiogenesis by promoting endothelial cell migration and tubulogenesis through upregulation of MT1-MMP

Robinet

Fahem

Cauchard

et al. 2005

Journal of Cell Science

219

172

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Elastin-derived peptides display a wide range of biological activities in a number of normal and transformed cells but their involvement in angiogenesis has not been reported. In the present study, we show that κ-elastin and VGVAPG hexapeptide elastin motif accelerated angiogenesis in the chick chorio-allantoic membrane in an in vivo model. They also stimulated pseudotube formation from human vascular and microvascular endothelial cells in the matrigel and collagen models as well as cell migration in an in vitro wound healing assay. Confocal and scanning electron microscopy analyses revealed the main reorganization of actin filaments mediated by elastin-derived peptides and changes in cell shape that correlated with a decrease of the cell form factor determined by computerized image analysis. Such elastin-derived peptide effects were attributed to upregulation of proMT1-MMP and proMMP-2 expression and activation at both the mRNA and protein levels. Batimastat, an inhibitor of furin convertase and TIMP-2, but not TIMP-1, totally abolished the influence of elastin-derived peptides (EDPs) on cell migration and tubulogenesis, thus favoring the involvement of MT1-MMP in such processes. To assess its contribution to EDP-mediated angiogenesis further, we used a small interfering RNA (siRNA) approach for specifically silencing MT1-MMP in human microvascular endothelial cells. Four sets of 21 bp siRNA duplexes targeting MT1-MMP mRNA were synthesized by in vitro transcription. Two of them proved to inhibit MT1-MMP expression efficiently but did not affect MT2-, MT3- and MT5-MMP expression. Seventy-two hours after transfection with 25 nM siRNAs EDP-induced MT1-MMP expression at the mRNA and protein levels was decreased fourfold. In parallel, proMMP-2 activation was inhibited. A scrambled siRNA, used as a negative control, had no effect. Finally, the effect of elastin peptides on pseudotube formation in MT1-MMP-siRNA transfected cells was totally abolished. These data emphasise the crucial role of MT1-MMP in the elastin-induced angiogenic phenotype of endothelial cells.

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“…To support this idea, microfibrils and RGD-containing fibrillin-1 fragments are already known to enhance adhesion, spreading, and migration of several cell types (5,6,14,47,53,54,61,70). Further support to this hypothesis was provided by 1) evidence that mice mutated for other microfibrillar components, e.g., fibulin-5 or emilin-1, have severe anomalies of vascular development and structure (51,73,74), and 2) the facts that mutations in the other main component of elastic fibers, elastin, cause Williams syndrome, and elastin fragments and tropoelastin have already been shown to influence Ca 2ϩ signaling, proliferation, and other functions in vascular and other types of cells (17,19,27,28,33,49,68).…”

Section: Discussionmentioning

confidence: 99%

Microfibrils and fibrillin-1 induce integrin-mediated signaling, proliferation and migration in human endothelial cells

Mariko

Ghandour

Raveaud

et al. 2010

American Journal of Physiology-Cell Physiology

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Growth Stimulation of Human Skin Fibroblasts by Elastin-Derived Peptides

Cited by 92 publications

References 20 publications

Signaling Pathways Transduced through the Elastin Receptor Facilitate Proliferation of Arterial Smooth Muscle Cells

Signaling Pathways Transduced through the Elastin Receptor Facilitate Proliferation of Arterial Smooth Muscle Cells

Elastin-derived peptides enhance angiogenesis by promoting endothelial cell migration and tubulogenesis through upregulation of MT1-MMP

Microfibrils and fibrillin-1 induce integrin-mediated signaling, proliferation and migration in human endothelial cells

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