| Project/Area Number |
25461376
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Osaka City University |
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Principal Investigator |
SHIOI ATSUSHI 大阪市立大学, 大学院医学研究科, 講師 (90260801)
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| Co-Investigator(Kenkyū-buntansha) |
SHOJI Tetsuo 大阪市立大学, 大学院医学研究科, 准教授 (40271192)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | マクロファージ / HIF-1 / オンコスタチンM / LPS / 動脈硬化 / 血管石灰化 / オンコスタチンＭ / 血管平滑筋細胞 / 骨芽細胞 / ＪＡＫ３ / STAT3 / ＨＩＦ－１ / ＬＰＳ |
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| Outline of Final Research Achievements |
We investigated the roles of hypoxia inducible factor 1 (HIF-1) in the development of atherosclerotic plaque calcification. In apoE-deficient mice, immunohistochemical staining revealed that macrophages are localized in hypoxic areas of atherosclerotic plaque lesions and that oncostatin M (OSM) is expressed in theses macrophages. Next, we investigated the stimulatory effects of OSM on osteoblastic differentiation of human vascular smooth muscle cells (HVSMC). OSM promoted osteoblastic differentiation of HVSMC through JAK3/STAT3 signaling pathway as evidenced by the experiments using specific inhibitor reagents and siRNAs. Finally, we examined the roles of HIF-1 in LPS-induced OSM expression in macrophages. The experiments utilizing inhibitors, hypoxia mimetics, and siRNA clarified that HIF-1 inhibits LPS-induced OSM expression in macrophages. These data suggest that HIF-1 in macrophages may play an inhibitory role in plaque calcification through inhibiting expression of OSM.
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