2004
DOI: 10.1074/jbc.m313462200
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Disialoganglioside (GD3) Synthase Gene Expression Suppresses Vascular Smooth Muscle Cell Responses via the Inhibition of ERK1/2 Phosphorylation, Cell Cycle Progression, and Matrix Metalloproteinase-9 Expression

Abstract: Sialic acid-containing glycosphingolipids (gangliosides) have been implicated in the regulation of various biological phenomena such as atherosclerosis. Recent report suggests that exogenously supplied disialoganglioside (GD3) serves a dual role in vascular smooth muscle cells (VSMC) proliferation and apoptosis. However, the role of the GD3 synthase gene in VSMC responses has not yet been elucidated. To determine whether a ganglioside is able to modulate VSMC growth, the effect of overexpression of the GD3 syn… Show more

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Cited by 69 publications
(81 citation statements)
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“…In particular, up-regulation of MMP expression has been reported to be dependent on activation of the raf/MEK/ERK signaling pathway, which strictly regulates gene expression (31)(32)(33). Consistently, whereas the high expression of MMP-2 and MMP-9 in C-26 cells correlates with constitutive activation of ERK1/2 protein kinases (Fig.…”
Section: Discussionsupporting
confidence: 48%
“…In particular, up-regulation of MMP expression has been reported to be dependent on activation of the raf/MEK/ERK signaling pathway, which strictly regulates gene expression (31)(32)(33). Consistently, whereas the high expression of MMP-2 and MMP-9 in C-26 cells correlates with constitutive activation of ERK1/2 protein kinases (Fig.…”
Section: Discussionsupporting
confidence: 48%
“…It has recently been shown that ganglioside GM3 inhibited MMP-9 expression induced by fibronectin or epidermal growth factor (EGF) in SCC12 carcinoma cells (21). In addition, the present results are in agreement with a previous report showing the inhibition of MMP-9 expression in GD3 synthase gene transfectants (33). However, the differences in the effects of the molecular action mechanisms of the GM3 and the GD3 synthase genes remain to be elucidated.…”
Section: Discussionsupporting
confidence: 82%
“…Studies have shown that GM1 and GM2 induce VSMC proliferation through ERK1/2 activation (31). Several studies have shown a dual function of ganglioside GD3, in both cell proliferation and inhibition of cell growth in VSMC (32,33). A number of studies have demonstrated massive and excessive accumulation of GM3 in atherosclerotic lesions (23,24).…”
Section: Discussionmentioning
confidence: 99%
“…Numerous studies have demonstrated that JNK1/2 and ERK1/2 transcriptionally regulate the expression of MMP-2 and MMP-9, which results in regulation of cell migration and invasion (25)(26)(27). In human bladder cancer cells, upregulation of the MAPK pathways may result in migration and regulation of the expression levels of MMPs (28).…”
Section: Discussionmentioning
confidence: 99%