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KAKEN_15H04825seika.pdf
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:280.8 KB
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:Aug 18, 2023 |
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Total downloads since Aug 18, 2023 : 583
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| Title |
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加齢とメタボリックシンドロームに伴う心血管障害に共通の分子基盤の解明
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| Kana |
カレイ ト メタボリック シンドローム ニ トモナウ シンケツカン ショウガイ ニ キョウツウ ノ ブンシ キバン ノ カイメイ
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Karei to metaborikku shindorōmu ni tomonau shinketsukan shōgai ni kyōtsū no bunshi kiban no kaimei
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Elucidation of molecular basis common to cardiovascular disorders associated with aging and metabolic syndrome
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佐野, 元昭
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サノ, モトアキ
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Sano, Motoaki
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慶應義塾大学・医学部(信濃町)・准教授
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Research team head
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科研費研究者番号 : 30265798
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白川, 公亮
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シラカワ, コウスケ
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Shirakawa, Kosuke
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Research team member
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山本, 恒久
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ヤマモト, ツネヒサ
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Yamamoto, Tsunehisa
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Research team member
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2018
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科学研究費補助金研究成果報告書
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2017
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肥満が見た目だけでなく内臓の老化を加速させるメカニズムを解明した。高脂肪食負荷マウスの内臓脂肪でCD4 T細胞の一部(CD44hiCD62LloCD4+ T細胞)が, 本来加齢マウスで出現する細胞老化の性質を獲得すること, この細胞老化がB細胞依存的に起こること, さらに, Senescence associated secretory phenotype (SASP)としてのオステオポンチンの大量分泌を介して, 内臓脂肪組織の慢性炎症と全身のインスリン抵抗性に関与していることを発見した。今後, 老化したTリンパ球集団を標的とした生活習慣病の発症予防をめざす治療法の開発につながることが期待される。
Chronic inflammation in visceral adipose tissue (VAT) precipitates the development of cardiometabolic disorders. Here, we have determined that a high-fat diet (HFD) caused a preferential increase and accumulation of CD44hiCD62LloCD4+ T cells that constitutively express PD-1 and CD153 in VAT. These cells possessed characteristics of cellular senescence and produced large amounts of osteopontin (OPN) in a PD-1-resistant manner. The features of these T cells were highly reminiscent of senescence-associated CD4+ T cells that normally increase with age. Adoptive transfer of CD153+PD-1+CD44hiCD4+ T cells from HFD-fed WT, but not Spp1-deficient, mice into the VAT of lean mice fed a normal diet recapitulated the essential features of VAT inflammation and insulin resistance. Our results demonstrate that a distinct CD153+PD-1+CD44hiCD4+ T cell population causes VAT inflammation by producing large amounts of OPN. This finding suggests a link between visceral adiposity and immune aging.
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研究種目 : 基盤研究(B)(一般)
研究期間 : 2015～2017
課題番号 : 15H04825
研究分野 : 内科学, 循環器, 心臓
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| History |
| Nov 12, 2018 | | インデックス を変更 |
| Aug 18, 2023 | | Creator 著者ID,Creator Name,Creator Kana,Creator Romanization,Creator Affiliation,Creator Affiliation (Translated),Creator Role,Creator Link,Abstract 内容,Note 注記 を変更 |
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