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KAKEN_23591200seika.pdf
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慢性腎臓病の血管石灰化発症機序における転写調節因子の役割の解明と治療への応用
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マンセイ ジンゾウビョウ ノ ケッカン セッカイカ ハッショウ キジョ ニ オケル テンシャ チョウセツ インシ ノ ヤクワリ ノ カイメイ ト チリョウ エノ オウヨウ
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Mansei jinzobyo no kekkan sekkaika hassho kijo ni okeru tensha chosetsu inshi no yakuwari no kaimei to chiryo eno oyo
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The studies on the roles of transcriptional factors in pathogenesis of vascular calcification by chronic kidney disease and their application for the therapy
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林, 松彦
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ハヤシ, マツヒコ
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Hayashi, Matsuhiko
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慶應義塾大学・医学部・教授
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Research team head
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科研費研究者番号 : 60129608
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吉田, 理
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ヨシダ, タダシ
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Yoshida, Tadashi
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慶應義塾大学・医学部・講師
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Research team member
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科研費研究者番号 : 00306713
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2014
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科学研究費補助金研究成果報告書
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2013
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慢性腎臓病患者にみられる動脈石灰化のメカニズム解明のために、本研究では、培養細胞およびモデル動物を用いて、動脈石灰化に関わる転写調節因子の役割を検討した。
高リン血症による血管平滑筋細胞の骨様細胞への形質変換に転写因子KLF4が関与することを、in vivo、in vtiroで同定した。また、同様の系で高血糖が血管石灰化の増悪因子として有意では無いことを示し、さらに血管平滑筋細胞特異的にNF-κB活性を抑制するマウスでは血管傷害による内膜肥厚性動脈硬化形成が抑制されることを示した。現在、腎不全病態におけるNF-κBの血管石灰化への役割をこれらマウスで用いて検討中である。
To reveal the mechanisms which induce vascular calcification in the patients with chronic kidney disease, roles of transcriptional factors which are related to vascular calcification are studied in the present study. We found that Klf4, a transcriptional factor, plays important roles in transformation of vascular smooth muscle cells to osteocyte-like cells by hyperphosphathemia in the in vivo and in vitro experiments. It was also shown that by the same experimental system hyperglycemia is not a significant factor for worsening of vascular calcification. In addition, by vascular smooth muscle cell specific inactivation of NF-kB activity in mouse, endothelial thickening arteriosclerosis by vascular injury was ameliorated. Currently, we are examining the roles of NF-kB in the pathogenesis of vascular calcification by chronic renal failure, using these genetically modified mouse.
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研究種目 : 基盤研究(C)
研究期間 : 2011～2013
課題番号 : 23591200
研究分野 : 医歯薬学
科研費の分科・細目 : 内科系臨床医学・腎臓内科学
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