Overexpression of membrane sialic acid-specific sialidase Neu3 inhibits matrix metalloproteinase-9 expression in vascular smooth muscle cells

Journal Article · Fri May 11 04:00:00 EDT 2007 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2007.02.155· OSTI ID:20991331

Moon, Sung-Kwon ^[1]; Cho, Seung-Hak ^[1]; Kim, Kyung-Woon ^[1]; Jeon, Jae Heung ^[2]; Ko, Jeong-Heon ^[2]; Kim, Bo Yeon ^[2]; Kim, Cheorl-Ho ^[1]

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1. Molecular and Cellular Glycobiology Unit, Department of Biological Science, Sungkyunkwan University, Chunchun-Dong 300, Suwon City, Kyunggi-Do 440-746 (Korea, Republic of)
2. Laboratory of Cellular Signaling Modulators, Plant Cell Biotechnology and Systemic Proteome Center, Korea Research Institute of Bioscience and Biotechnology, 9 Yusong, Daejeon 305-600 (Korea, Republic of)

The ganglioside-specific sialidase Neu3 has been suggested to participate in cell growth, migration, and differentiation. Recent reports suggest that sialidase may be involved in intimal thickening, an early stage in the development of atherosclerosis. However, the role of the Neu3 gene in vascular smooth muscle cells (VSMC) responses has not yet been elucidated. To determine whether a Neu3 is able to modulate VSMC growth, the effect of overexpression of the Neu3 gene on cell proliferation was examined. However, the results show that the overexpression of this gene has no effect on DNA synthesis and ERK phosphorylation in cultured VSMC in the presence of TNF-{alpha}. Because atherogenic effects need not be limited to proliferation, we decided to examine whether Neu3 exerted inhibitory effects on matrix metalloproteinase-9 (MMP-9) activity in TNF-{alpha}-induced VSMC. The expression of the Neu3 gene led to the inhibition of TNF-{alpha}-induced matrix metalloproteinase-9 (MMP-9) expression in VSMC as determined by zymography and immunoblot. Furthermore, Neu3 gene expression strongly decreased MMP-9 promoter activity in response to TNF-{alpha}. This inhibition was characterized by the down-regulation of MMP-9, which was transcriptionally regulated at NF-{kappa}B and activation protein-1 (AP-1) sites in the MMP-9 promoter. These findings suggest that the Neu3 gene represents a physiological modulator of VSMC responses that may contribute to plaque instability in atherosclerosis.

• OSTI ID: 20991331
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 356; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ARTERIOSCLEROSIS
CELL MEMBRANES
CELL PROLIFERATION
DNA
GENE REGULATION
GENES
GROWTH
INHIBITION
MUSCLES
PHOSPHORYLATION
PROMOTERS
PROTEINS
SIALIC ACID