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Tumor necrosis factor-α increases alkaline phosphatase expression in vascular smooth muscle cells via MSX2 induction
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Hye-Lim | - |
dc.contributor.author | Woo, Kyung Mi | - |
dc.contributor.author | Ryoo, Hyun-Mo | - |
dc.contributor.author | Baek, Jeong-Hwa | - |
dc.date.accessioned | 2011-10-14T04:18:06Z | - |
dc.date.available | 2011-10-14T04:18:06Z | - |
dc.date.issued | 2010-01 | - |
dc.identifier.citation | Biochemical and Biophysical Research Communications 2010;391:1087-1092 | en |
dc.identifier.issn | 0006-291X | - |
dc.identifier.uri | https://hdl.handle.net/10371/74145 | - |
dc.description.abstract | Vascular calcification is implicated in many diseases including atherosclerosis and diabetes. Tumor necrosis factor-α (TNF-α) has been shown to promote vascular calcification both in vitro and in vivo. However, the molecular mechanism of TNF-α-mediated vascular calcification has not yet been fully defined. Therefore, in this study, we aimed to investigate whether MSX2 acts as a crucial regulator in TNF-α-induced vascular calcification and to define the regulatory mechanism of MSX2 induction in human vascular smooth muscle cells (VSMCs). TNF-α increased the expression of osteogenic marker genes including RUNX2, osterix, alkaline phosphatase (ALP), and bone sialoprotein, and it also promoted matrix mineralization in VSMCs. In addition, TNF-α enhanced MSX2 expression in a dose- and time-dependent manner. MSX2 over-expression alone induced ALP expression, whereas knockdown of MSX2 with small interfering RNA completely blocked TNF-α-induced ALP expression. New protein synthesis was dispensable for MSX2 induction by TNF-α, and the inhibition of NF-κB by BAY-11-7082 or by dominant negative IκBα abolished the TNF-α-directed induction of MSX2 expression. However, inhibition of NADPH oxidase did not affect MSX2 expression. In conclusion, our study suggests that TNF-α directly induces MSX2 expression through the NF-κB pathway, which in turn induces expression of ALP, a key molecule in mineralization, in VSMCs. | en |
dc.description.sponsorship | This work was supported by the Basic Research Program of the Korea Science & Engineering Foundation (R01-2005-000-106650)
and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (KRF-2006-000-E00093). | en |
dc.language.iso | en | en |
dc.publisher | Elsevier | en |
dc.subject | Vascular smooth muscle cells | en |
dc.subject | Tumor necrosis factor-α | en |
dc.subject | MSX2 | en |
dc.subject | NF-κB | en |
dc.subject | Alkaline phosphatase | en |
dc.title | Tumor necrosis factor-α increases alkaline phosphatase expression in vascular smooth muscle cells via MSX2 induction | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 이혜림 | - |
dc.contributor.AlternativeAuthor | 우경미 | - |
dc.contributor.AlternativeAuthor | 류현모 | - |
dc.contributor.AlternativeAuthor | 백정화 | - |
dc.identifier.doi | 10.1016/j.bbrc.2009.12.027 | - |
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