2024/02/28 更新

写真a

イノウエ アイコ
井上 愛子
INOUE Aiko
所属
未来社会創造機構 ナノライフシステム研究所 マイクロ・ナノメカトロニクス研究部門 特任講師
大学院医学系研究科 特任講師
職名
特任講師
外部リンク

学位 1

  1. 博士(医学) ( 2017年3月   名古屋大学 ) 

学歴 2

  1. 名古屋大学   大学院医学系研究科 総合医学専攻博士課程

    - 2017年3月

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    国名: 日本国

  2. 浜松医科大学   大学院医学系研究科看護学専攻修士課程

    - 2003年3月

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    国名: 日本国

所属学協会 2

  1. 日本サルコペニア・フレイル学会   評議員

  2. 日本老年医学会

委員歴 4

  1. 豊山町地域包括支援センター運営協議会委員  

    2121年8月   

  2. 豊山町健康づくり審議会委員  

    2022年7月   

  3. 豊山町地域包括支援センター   豊山町地域包括ケアシステム推進協議会  

    2022年7月   

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    団体区分:自治体

  4. 豊山町総合計画審議会委員  

    2018年11月   

受賞 2

  1. 第4回日本サルコペニア・フレイル学会大会最優秀演題賞

    2017年10月   第4回日本サルコペニア・フレイル学会大会  

    井上愛子、成憲武、朴麗梅、五藤大貴、小笠原真雄、葛谷雅文

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    受賞区分:国内学会・会議・シンポジウム等の賞  受賞国:日本国

  2. 第3回日本自律神経学会賞(基礎部門優秀論文賞)

    2006年11月   日本自律神経学会   食事摂取と体位が健常者の核心温ならびに血圧に及ぼす影響―炭水化物摂取と仰臥位・長坐位における検討―

    長谷川愛子、伊藤 剛、 石津みゑ子、 花輪壽彦

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    受賞区分:国内学会・会議・シンポジウム等の賞  受賞国:日本国

 

論文 62

  1. Cathepsin S activity controls chronic stress-induced muscle atrophy and dysfunction in mice

    Wan, Y; Piao, LM; Xu, SN; Meng, XK; Huang, Z; Inoue, A; Wang, HL; Yue, XL; Jin, XY; Nan, YS; Shi, GP; Murohara, T; Umegaki, H; Kuzuya, M; Cheng, XW

    CELLULAR AND MOLECULAR LIFE SCIENCES   80 巻 ( 9 ) 頁: 254   2023年9月

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    記述言語:英語   出版者・発行元:Cellular and Molecular Life Sciences  

    Exposure to chronic psychological stress (CPS) is an intractable risk factor for inflammatory and metabolic diseases. Lysosomal cysteinyl cathepsins play an important role in human pathobiology. Given that cathepsin S (CTSS) is upregulated in the stressed vascular and adipose tissues, we investigated whether CTSS participates in chronic stress-induced skeletal muscle mass loss and dysfunction, with a special focus on muscle protein metabolic imbalance and apoptosis. Eight-week-old male wildtype (CTSS+/+) and CTSS-knockout (CTSS−/−) mice were randomly assigned to non-stress and variable-stress groups. CTSS+/+ stressed mice showed significant losses of muscle mass, dysfunction, and fiber area, plus significant mitochondrial damage. In this setting, stressed muscle in CTSS+/+ mice presented harmful alterations in the levels of insulin receptor substrate 2 protein content (IRS-2), phospho-phosphatidylinositol 3-kinase, phospho-protein kinase B, and phospho-mammalian target of rapamycin, forkhead box-1, muscle RING-finger protein-1 protein, mitochondrial biogenesis-related peroxisome proliferator-activated receptor-γ coactivator-α, and apoptosis-related B-cell lymphoma 2 and cleaved caspase-3; these alterations were prevented by CTSS deletion. Pharmacological CTSS inhibition mimics its genetic deficiency-mediated muscle benefits. In C2C12 cells, CTSS silencing prevented stressed serum- and oxidative stress-induced IRS-2 protein reduction, loss of the myotube myosin heavy chain content, and apoptosis accompanied by a rectification of investigated molecular harmful changes; these changes were accelerated by CTSS overexpression. These findings demonstrated that CTSS plays a role in IRS-2-related protein anabolism and catabolism and cell apoptosis in stress-induced muscle wasting, suggesting a novel therapeutic strategy for the control of chronic stress-related muscle disease in mice under our experimental conditions by regulating CTSS activity.

    DOI: 10.1007/s00018-023-04888-4

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  2. Myonectin protects against skeletal muscle dysfunction in male mice through activation of AMPK/PGC1α pathway

    Ozaki, Y; Ohashi, K; Otaka, N; Kawanishi, H; Takikawa, T; Fang, LX; Takahara, K; Tatsumi, M; Ishihama, S; Takefuji, M; Kato, K; Shimizu, Y; Bando, YK; Inoue, A; Kuzuya, M; Miura, S; Murohara, T; Ouchi, N

    NATURE COMMUNICATIONS   14 巻 ( 1 ) 頁: 4675   2023年8月

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    記述言語:英語   出版者・発行元:Nature Communications  

    To maintain and restore skeletal muscle mass and function is essential for healthy aging. We have found that myonectin acts as a cardioprotective myokine. Here, we investigate the effect of myonectin on skeletal muscle atrophy in various male mouse models of muscle dysfunction. Disruption of myonectin exacerbates skeletal muscle atrophy in age-associated, sciatic denervation-induced or dexamethasone (DEX)-induced muscle atrophy models. Myonectin deficiency also contributes to exacerbated mitochondrial dysfunction and reduces expression of mitochondrial biogenesis-associated genes including PGC1α in denervated muscle. Myonectin supplementation attenuates denervation-induced muscle atrophy via activation of AMPK. Myonectin also reverses DEX-induced atrophy of cultured myotubes through the AMPK/PGC1α signaling. Furthermore, myonectin treatment suppresses muscle atrophy in senescence-accelerated mouse prone (SAMP) 8 mouse model of accelerated aging or mdx mouse model of Duchenne muscular dystrophy. These data indicate that myonectin can ameliorate skeletal muscle dysfunction through AMPK/PGC1α-dependent mechanisms, suggesting that myonectin could represent a therapeutic target of muscle atrophy.

    DOI: 10.1038/s41467-023-40435-2

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  3. Cathepsin S deficiency improves muscle mass loss and dysfunction via the modulation of protein metabolism in mice under pathological stress conditions

    Wan, Y; Piao, LM; Xu, SN; Inoue, A; Meng, XK; Lei, YN; Huang, Z; Wang, HL; Yue, XL; Shi, GP; Kuzuya, M; Cheng, XW

    FASEB JOURNAL   37 巻 ( 8 ) 頁: e23086   2023年8月

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    記述言語:英語   出版者・発行元:FASEB Journal  

    Cathepsin S (CTSS) is a widely expressed cysteinyl protease that has garnered attention because of its enzymatic and non-enzymatic functions under inflammatory and metabolic pathological conditions. Here, we examined whether CTSS participates in stress-related skeletal muscle mass loss and dysfunction, focusing on protein metabolic imbalance. Eight-week-old male wildtype (CTSS+/+) and CTSS-knockout (CTSS−/−) mice were randomly assigned to non-stress and variable-stress groups for 2 weeks, and then processed for morphological and biochemical studies. Compared with non-stressed mice, stressed CTSS+/+ mice showed significant losses of muscle mass, muscle function, and muscle fiber area. In this setting, the stress-induced harmful changes in the levels of oxidative stress-related (gp91phox and p22phox,), inflammation-related (SDF-1, CXCR4, IL-1β, TNF-α, MCP-1, ICAM-1, and VCAM-1), mitochondrial biogenesis-related (PPAR-γ and PGC-1α) genes and/or proteins and protein metabolism-related (p-PI3K, p-Akt, p-FoxO3α, MuRF-1, and MAFbx1) proteins; and these alterations were rectified by CTSS deletion. Metabolomic analysis revealed that stressed CTSS−/− mice exhibited a significant improvement in the levels of glutamine metabolism pathway products. Thus, these findings indicated that CTSS can control chronic stress-related skeletal muscle atrophy and dysfunction by modulating protein metabolic imbalance, and thus CTSS was suggested to be a promising new therapeutic target for chronic stress-related muscular diseases.

    DOI: 10.1096/fj.202300395RRR

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  4. CTSS Modulates Stress-Related Carotid Artery Thrombosis in a Mouse FeCl<sub>3</sub> Model

    Xu, SN; Piao, LM; Wan, Y; Huang, Z; Meng, XK; Inoue, A; Wang, HL; Yue, XL; Jin, XL; Shi, GP; Kuzuya, M; Cheng, XW

    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY   43 巻 ( 7 ) 頁: E238 - E253   2023年7月

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    記述言語:英語   出版者・発行元:Arteriosclerosis, Thrombosis, and Vascular Biology  

    Background: Exposure to chronic psychological stress is a risk factor for metabolic cardiovascular disease. Given the important role of lysosomal CTSS (cathepsin S) in human pathobiology, we examined the role of CTSS in stress-related thrombosis, focusing on inflammation, oxidative stress, and apoptosis. Methods: Six-week-old wild-type mice (CTSS+/+) and CTSS-deficient mice (CTSS-/-) randomly assigned to nonstress and 2-week immobilization stress groups underwent iron chloride3 (FeCl3)-induced carotid thrombosis surgery for morphological and biochemical studies. Results: On day 14 poststress/surgery, stress had increased the lengths and weights of thrombi in the CTSS+/+mice, plus harmful changes in the levels of PAI-1 (plasminogen activation inhibitor-1), ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 13 motifs), and vWF (von Willebrand factor) and arterial tissue CTSS expression. Compared to the nonstressed CTSS+/+mice, the stressed CTSS-/-mice had decreased levels of PAI-1, vWF, TNF (tumor necrosis factor)-α, interleukin-1β, toll-like receptor-4, cleaved-caspase 3, cytochrome c, p16INK4A, gp91phox, p22phox, ICAM-1 (intercellular adhesion molecule-1), MCP-1 (monocyte chemoattractant protein-1), MyD88 (myeloid differentiation primary response 88), and MMP (matrix metalloproteinase)-2/-9 and increased levels of ADAMTS13, SOD (superoxide dismutase)-1/-2, eNOS (endothelial NO synthase), p-Akt (phospho-protein kinase B), Bcl-2 (B-cell lymphoma-2), p-GSK3α/β (phospho-glycogen synthase kinases alpha and beta), and p-Erk1/2 (phospho-extracellular signal-regulated kinase 1 and 2) mRNAs and/or proteins. CTSS deletion also reduced the arterial thrombus area and endothelial loss. A pharmacological inhibition of CTSS exerted a vasculoprotective action. In vitro, CTSS silencing and overexpression, respectively, reduced and increased the stressed serum and oxidative stress-induced apoptosis of human umbilical vein endothelial cells, and they altered apoptosis-related proteins. Conclusions: CTSS inhibition appeared to improve the stress-related thrombosis in mice that underwent FeCl3-induction surgery, possibly by reducing vascular inflammation, oxidative stress, and apoptosis. CTSS could thus become a candidate therapeutic target for chronic psychological stress-related thrombotic events in metabolic cardiovascular disease.

    DOI: 10.1161/ATVBAHA.122.318455

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  5. Cathepsins in the extracellular space: Focusing on non-lysosomal proteolytic functions with clinical implications

    Wang, HL; Inoue, A; Lei, YN; Wu, HX; Hong, L; Cheng, XW

    CELLULAR SIGNALLING   103 巻   頁: 110531   2023年3月

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    記述言語:英語   出版者・発行元:Cellular Signalling  

    Cathepsins can be found in the extracellular space, cytoplasm, and nucleus. It was initially suspected that the primary physiological function of the cathepsins was to break down intracellular protein, and that they also had a role in pathological processes including inflammation and apoptosis. However, the many actions of cathepsins outside the cell and their complicated biological impacts have garnered much interest. Cathepsins play significant roles in a number of illnesses by regulating parenchymal cell proliferation, cell migration, viral invasion, inflammation, and immunological responses through extracellular matrix remodeling, signaling disruption, leukocyte recruitment, and cell adhesion. In this review, we outline the physiological roles of cathepsins in the extracellular space, the crucial pathological functions performed by cathepsins in illnesses, and the recent breakthroughs in the detection and therapy of specific inhibitors and fluorescent probes in associated dysfunction.

    DOI: 10.1016/j.cellsig.2022.110531

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書籍等出版物 1

  1. 最先端ナノライフシステム研究

    ( 担当: 分担執筆 ,  範囲: 4章 健康寿命の延伸に関する実装研究)

    丸善プラネット株式会社  2022年3月  ( ISBN:978-4-86345-520-7

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    総ページ数:215   担当ページ:63-69   記述言語:日本語 著書種別:教科書・概説・概論

MISC 4

  1. (特集 老化・フレイルとサルコペニア) フレイル・サルコペニアとバイオマーカー

    井上愛子、葛谷雅文、成 憲武  

    CLINICAL CALCIUM28 巻 ( 9 ) 頁: 1191 - 1200   2018年8月

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    担当区分:筆頭著者   記述言語:日本語  

  2. (老年医学の展望) サルコペニアの分子メカニズム

    井上愛子、成 憲武、五籐大貴、葛谷雅文  

    日本老年医学会雑誌55 巻   頁: 13 - 24   2018年

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  3. 冠動脈硬化の新しい分子機序:炎症•免疫からみた最新の知見

    成 憲武、井上愛子  

    医学の歩み259 巻 ( 6 ) 頁: 590 - 596   2016年

  4. (特集 高齢者医療におけるサルコペニア・フレイル対策) サルコペニア・フレイルのバイオマーカー

    井上愛子、成 憲武、葛谷雅文  

    医薬ジャーナル51 巻 ( 9 ) 頁: 67 - 71   2015年9月

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    担当区分:筆頭著者  

    DOI: https://doi.org/10.20837/1201509051

講演・口頭発表等 16

  1. Cathepsin K activity controls injury-related vascular repair in mice

    Hu L., Cheng X.W., Song H., Inoue A., Jiang H., Li X., Shi G.P., Kozawa E., Okumura K., Kuzuya M.

    Hypertension  2014年3月  Hypertension

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    記述言語:日本語  

    Cathepsin K (CatK) is one of the most potent mammalian collagenases. We showed previously the increased expression of CatK in human and animal atherosclerotic lesions. Here, we hypothesized that ablation of CatK mitigates injury-induced neointimal hyperplasia. Male wild-type (CatK) and CatK-deficient (CatK) mice underwent ligation or a combination of ligation and polyethylene cuff-replacement injuries to the right common carotid artery just proximal to its bifurcation, and they were then processed for morphological and biochemical studies at specific time points. On operative day 28, CatK significantly reduced neointimal formation and neovessel formation in both single- and combination-injured arteries compared with the Cat K mice. At early time points, CatK reduced the lesion macrophage contents and medial smooth muscle cell proliferation, the mRNA levels of monocyte chemoattractant protein-1, toll-like receptor-2, toll-like receptor-4, chemokine ligand-12, and the gelatinolytic activity related to matrix metalloproteinase-2/-9. An aorta-explant assay revealed that smooth muscle cell movement was impaired in the CatK mice compared with the CatK mice. In addition, the smooth muscle cells and macrophages from CatK mice had less invasive ability through a reconstituted basement membrane barrier. This vasculoprotective effect was mimicked by Cat inhibition with trans-epoxysuccinyl-L-leucylamido-{4-guanidino} butane (E64d). These results demonstrate an essential role of CatK in neointimal lesion formation in response to injury, possibly via the reduction of toll-like receptor-2/-4-mediated inflammation and smooth muscle cell proliferation, suggesting a novel therapeutic strategy for the control of endovascular treatment-related restenosis by regulating CatK activity. © 2013 American Heart Association, Inc.

    DOI: 10.1161/HYPERTENSIONAHA.113.02141

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  2. 中核温ならびに自律神経機能よりみた「四肢型冷え症」の病態(03 病態(現代医学)(1))

    伊藤 剛, 長谷川 愛子, 高橋 裕子, 花輪 壽彦

    日本東洋醫學雜誌  2004年5月  社団法人日本東洋医学会

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    記述言語:日本語  

    CiNii Research

  3. 「食後佳眠倦怠」の病態解析(第1報) : 健常者における食後傾眠について(02病態(伝統医学)(1))

    長谷川 愛子, 伊藤 剛, 花輪 壽彦

    日本東洋醫學雜誌  2003年4月  社団法人日本東洋医学会

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    記述言語:日本語  

    CiNii Research

  4. Mechanisms Underlying the Impairment of Ischemia-induced Neovascularization in Aging Mice : the Pivotal Role for Matirx-Metalloproteinase-2(Regeneration(angiogenesis/myocardial regeneration)

    Cheng Xian Wu, Kuzuya Masafumi, Okumura Kenji, Inoue Aiko, Nakamura Kae, Sasaki Takeshi, Kim Veon, Yokota Mitsuhiro, Murohara Toyoaki

    The 72nd Annual Scientific Meeting of the Japanese Circulation Society  2008年3月1日  Japanese Circulation Society

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    記述言語:英語  

    CiNii Research

  5. Treatment of ApoE-Deficient Mice with Statin Inhibits the Oxidative Stress-dependent Lysosomal Protease Cathepsin Activation System : Implication for Plaque Stability

    Cheng Xian Wu, Kuzuya Masafumi, Nakamura Kae, Okumura Kenji, Inoue Aiko, Sasaki Takeshi, Yokota Mitsuhiro, Murohara Toyoaki

    The 72nd Annual Scientific Meeting of the Japanese Circulation Society  2008年3月1日  Japanese Circulation Society

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    記述言語:英語  

    CiNii Research

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科研費 3

  1. 独居高齢者に対するICTを活用した包括的フレイル予防システムの運用による介入効果

    研究課題/研究課題番号:21K17436  2021年4月 - 2024年3月

    科学研究費助成事業  若手研究

    井上 愛子

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    担当区分:研究代表者 

    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    世界に類を見ないスピードで超高齢社会を迎えている我が国において、ケアが必要な高齢者の絶対数の増加と現役世代の減少により医療・介護を担う人的資源が枯渇していく中で、持続可能なフレイルへの対策が急務となっている。
    本研究では、申請者らが2019年度に構築した循環型健康寿命延伸プログラムをスマートスピーカーを活用した独居高齢者向けのフレイル予防アプリケーション(独居高齢者見守りシステム)として新たに改良し、包括的フレイル予防支援システムによる独居高齢者の心身機能の維持・向上やフレイル予防効果ならびに健康行動促進要因を明らかにする。

  2. 超高齢社会における健康増進のためのICT/IoT利活用に関する研究

    研究課題/研究課題番号:21K12593  2021年4月 - 2024年3月

    科学研究費助成事業  基盤研究(C)

    浦田 真由, 安田 孝美, 井上 愛子

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    担当区分:研究分担者 

    超高齢社会において,高齢者の社会的孤立をいかに防ぐかは自治体の大きな課題となっているが,新型コロナウイルス感染症の影響により,地域での高齢者支援サービスの実施が困難となっている。本研究では,地域在住高齢者の健康増進のためのICT/IoT利活用を社会情報学と老年医学の学際研究として取り組み,地域への実装によってその効果を検証する。健康寿命を延ばすためのモデルを構築し,地域のICT/IoT 利活用を支える担い手の育成を行うことで,研究期間後も取り組みを継続させることを目指している。

  3. フレイルおよびサルコペニア予防のための骨格筋リモデリングと再生機構解明

    研究課題/研究課題番号:18K15414  2018年4月 - 2021年3月

    科学研究費助成事業  若手研究

    井上 愛子

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    担当区分:研究代表者 

    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    高齢期の骨格筋は障害を伴っていることが多く(サルコペニア、フレイルなど)、治療には骨格筋再生へのアプローチが必要である。細胞の分化・増殖、及びアポトーシスにおいて重要な役割を果たし、老化に伴いそのシグナル伝達の不活化が起こることが報告されているNotch シグナルとその活性化に関与するカテプシンKに着目し、サルコペニア形成、骨格筋のリモデリングや再生への関与を検討した。カテプシンKは、サルコペニアを代表とする骨格筋障害に関与することを明らかにした。
    カテプシンKが、カヘキシアモデルマウスの骨格筋の萎縮と機能障害にも関与している可能性が示唆されたことにより、今後は高齢者のQOLやADLの低下予防や、フレイルなどの改善のための新たな分子標的になる可能性が示唆された。