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Effect of skeletal muscle/fat-derived exosomes on diabetic microangiopathy by ultrasound irradiation

Research Project

Project/Area Number 19H03989
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 59010:Rehabilitation science-related
Research InstitutionNagoya Women's University

Principal Investigator

Kondo Hiroyo  名古屋女子大学, 健康科学部, 准教授 (50333183)

Co-Investigator(Kenkyū-buntansha) 藤野 英己  神戸大学, 保健学研究科, 教授 (20278998)
前重 伯壮  神戸大学, 保健学研究科, 准教授 (90617838)
石原 昭彦  京都大学, 人間・環境学研究科, 教授 (90184548)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2021: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2020: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Keywords微小血管 / 糖尿病 / エクソソーム / 骨格筋 / 超音波
Outline of Research at the Start

本研究課題では骨格筋細胞や脂肪細胞から放出される成分のうち,超音波照射により放出されるエクソソームの存在と作用を検出し,糖尿病モデル動物の骨格筋の微小血管障害に対する効果とエクソソームを介した作用効果を検証することを目的とした.また,本検証では共焦点レーザー法による毛細血管三次元構造,血管新生抑制に関連する因子等を解析し,これらの評価から糖尿病性微小血管障害に対するエクソソームによる超音波療法の効果と機序を検証し,糖尿病合併症の予防のための療法の開発を行う計画である.

Outline of Final Research Achievements

Complications of diabetes mellitus are thought to be caused by vascular endothelial injury and involve chronic microinflammation. In the present study, cultured skeletal muscle cells were irradiated with ultrasound and exosomes released from the cells were extracted. The exosomes were added to macrophages, and the functional changes of macrophages were examined. Ultrasound irradiation increased the released exosomes and attenuated inflammation of macrophages. In addition, the expression of IRG1, an immune response gene, was increased, and itaconic acid was increased. Furthermore, NRF2 expression was suppressed and was reduced inflammation. These results suggest that ultrasound irradiation can regulate inflammatory macrophages and may prevent complications caused by diabetes mellitus.

Academic Significance and Societal Importance of the Research Achievements

糖尿病における骨格筋の血管障害は重症化に関連し高齢化社会に大きな影響を及ぼしている。本研究課題では超音波照射により骨格筋細胞から放出されるエクソソームの存在と作用を明らかにし,超音波刺激の影響とその細胞間コミュニケーションのメカニズムを解明することによって,代謝障害に起因する疾患の予防や治療に細胞レベルの知見をもたらし,高齢化社会の健康寿命の延伸に寄与するものと考えられる。

Report

(4 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (46 results)

All 2023 2022 2021 2020 2019

All Journal Article (18 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 18 results) Presentation (28 results) (of which Int'l Joint Research: 9 results)

  • [Journal Article] Brazilian propolis intake decreases body fat mass and oxidative stress in community-dwelling elderly females: A randomized placebo-controlled trial.2023

    • Author(s)
      Kanazashi M, Iida T, Nakanishi R, Tanaka M, Ikeda H, Takamiya N, Maeshige N, Kondo H, Nishigami T, Harada T, Fujino H.
    • Journal Title

      Nutrients

      Volume: 15 Pages: 364-364

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acute effects of combination therapy by triceps surae stretching and electrical stimulation to the tibialis anterior on medial forefoot plantar pressure during gait in patients with diabetes mellitus.2023

    • Author(s)
      Maeshige N, Moriguchi M, Fujii M, Kanazawa H, Yoshikawa Y, Kitamura K, Okuno F, Yamaguchi A, Uemura M, Hosomi M, Hara K, Terashi H, Fujino H.
    • Journal Title

      Int J Low Extrem Wounds

      Volume: 2023 Pages: 153473462211484-153473462211484

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mild hyperbaric oxygen exposure enhances peripheral circulatory natural killer cells in healthy young women.2023

    • Author(s)
      Nisa BU, Nakanishi R, Tanaka M, Lin H, Hirabayashi T, Maeshige N, Kondo H, Fujino H.
    • Journal Title

      Life (Basel)

      Volume: 13 Pages: 408-408

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Skeletal myotube-derived extracellular vesicles enhance itaconate production and attenuate inflammatory responses of macrophages2023

    • Author(s)
      Yamaguchi A, Maeshige N, Yan J, Ma X, Uemura M, Matsuda M, Nishimura Y, Hasunuma T, Kondo H, Fujino H, Yuan ZM.
    • Journal Title

      Front Immunol

      Volume: 14 Pages: 1099799-1099799

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Impacts of astaxanthin supplementation on walking capacity by reducing oxidative stress in nursing home residents.2022

    • Author(s)
      Nakanishi R, Kanazashi M, Tanaka M, Tanaka M, Fujino H.
    • Journal Title

      Int J Environ Res Public Health

      Volume: 19 Pages: 13492-13492

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pulsed-Ultrasound Irradiation Induces the Production of Itaconate and Attenuates Inflammatory Responses in Macrophages.2022

    • Author(s)
      Yamaguchi A, Maeshige N, Ma X, Uemura M, Noguchi H, Matsuda M, Nishimura Y, Hasunuma T, Kondo H, Fujino H.
    • Journal Title

      J Inflamm Res.

      Volume: 13 Pages: 2387-2395

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of astaxanthin incorporation by pulsed high-intensity ultrasound in LPS-stimulated macrophages.2022

    • Author(s)
      Ma X, Yamaguchi A, Maeshige N, Uemura M, Noguchi H, Kondo H, Fujino H.
    • Journal Title

      J Med Ultrason

      Volume: 49 Pages: 125-132

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Time course of capillary regression and an expression balance between vascular endothelial growth factor-A and thrombospondin-1 in the soleus muscle of hindlimb unloaded rats.2022

    • Author(s)
      Tanaka M, Kanazashi M, Kondo H, Fujino H.
    • Journal Title

      Muscle Nerve.

      Volume: 65 Pages: 350-360

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pulsed ultrasound prevents lipopolysaccharide-induced muscle atrophy through inhibiting p38 MAPK phosphorylation in C2C12 myotubes.2021

    • Author(s)
      Ueno M, Maeshige N, Hirayama Y, Yamaguchi A, Ma X, Uemura M, Kondo H, Fujino H.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 17 Pages: 184-190

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High-intensity ultrasound irradiation promotes the release of extracellular vesicles from C2C12 myotubes.2021

    • Author(s)
      Maeshige N, Langston PK, Yuan ZM, Kondo H, Fujino H.
    • Journal Title

      Ultrasonics.

      Volume: 110 Pages: 106243-106243

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protective effects of chlorogenic acid on capillary regression caused by disuse muscle atrophy.2021

    • Author(s)
      Xing J, Pan H, Lin H, Nakanishi R, Hirabayashi T, Nakayama E, Ma X, Maeshige N, Kondo H, Fujino H.
    • Journal Title

      Biomed Res.

      Volume: 42 Pages: 257-264

    • NAID

      130008132076

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of combined treatment with blood flow restriction and low-current electrical stimulation on capillary regression in the soleus muscle of diabetic rats.2021

    • Author(s)
      Tanaka M, Morifuji T, Sugimoto K, Akasaka H, Fujimoto T, Yoshikawa M, Nakanishi R, Kondo H, Fujino H.
    • Journal Title

      J Appl Physiol.

      Volume: 131 Pages: 1219-1229

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduced metabolic capacity in fast and slow skeletal muscle via oxidative stress and the energy-sensing of AMPK/SIRT1 in malnutrition.2021

    • Author(s)
      Hirabayashi T, Nakanishi R, Tanaka M, Nisa BU, Maeshige N, Kondo H, Fujino H.
    • Journal Title

      Physiol Rep.

      Volume: 9 Pages: 14763-14763

    • NAID

      120007115801

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preventive effects of low-intensity endurance exercise for severe hyperglycemia-induced capillary regression in non-obese type 2 diabetes rat skeletal muscle.2021

    • Author(s)
      Morifuji T, Tanaka M, Nakanishi R, Hirabayashi T, Kondo H, Fujino H.
    • Journal Title

      Physiol Rep.

      Volume: 9 Pages: 14712-14712

    • NAID

      120006975820

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preventive effects of low-intensity endurance exercise for severe hyperglycemia-induced capillary regression in non-obese type 2 diabetes rat skeletal muscle.2021

    • Author(s)
      Morifuji T, Tanaka M, Nakanishi R, Hirabayashi T, Kondo H, Fujino H.
    • Journal Title

      Physiol Rep

      Volume: 9 Pages: 14712-14712

    • NAID

      120006975820

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pulsed ultrasound prevents lipopolysaccharide-induced muscle atrophy through inhibiting p38 MAPK phosphorylation in C2C12 myotubes.2021

    • Author(s)
      Ueno M, Maeshige N, Hirayama Y, Yamaguchi A, Ma X, Uemura M, Kondo H, Fujino H.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 17 Pages: 184-190

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of combined treatment with blood flow restriction and low-current electrical stimulation on capillary regression in the soleus muscle of diabetic rats.2021

    • Author(s)
      Tanaka M, Morifuji T, Sugimoto K, Akasaka H, Fujimoto T, Yoshikawa M, Nakanishi R, Kondo H, Fujino H.
    • Journal Title

      J Appl Physiol

      Volume: 131 Pages: 1219-1229

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protective effects of low-intensity exercise on metabolic oxidative capacity and capillarization in skeletal muscle of non-obese diabetic rats.2020

    • Author(s)
      Qatamish MA, Al-Nassan SM, Kondo H, Fujino H.
    • Journal Title

      Biomed Res.

      Volume: 41 Pages: 227-236

    • NAID

      130007927043

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] Ultrasound irradiation induces the production of itaconate and attenuates inflammatory responses in macrophages.2022

    • Author(s)
      Atomu Yamaguchi, Noriaki Maeshige, Xiaoqi Ma, Mikiko Uemura, Hikari Noguchi, Hiroyo Kondo, Hidemi Fujino.
    • Organizer
      39th Congress of the International Union of Physiological Sciences
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Metabolic patterns in myotubes after high-intensity ultrasound irradiation2022

    • Author(s)
      Xiaoqi Ma, Noriaki Maeshige, Atomu Yamaguchi, Mikiko Uemura, Hiroyo Kondo, Hidemi Fujino
    • Organizer
      39th Congress of the International Union of Physiological Sciences
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Protective effects of chlorogenic acid on capillary regression caused by disuse muscle atrophy.2022

    • Author(s)
      Jihao Xing, Han Pan, Ryosuke Nakanishi, Takumi Hirabayashi, Xiaoqi Ma, Noriaki Maeshige, Hiroyo Kondo, and Hidemi Fujino.
    • Organizer
      39th Congress of the International Union of Physiological Sciences
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Enhancement of astaxanthin incorporation by pulsed high-intensity ultrasound in LPS-stimulated macrophages.2022

    • Author(s)
      Xiaoqi Ma, Atomu Yamaguchi, Noriaki Maeshige, Mikiko Uemura, Hikari Noguchi, Hiroyo Kondo, Hidemi Fujino.
    • Organizer
      39th Congress of the International Union of Physiological Sciences
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) prevent inflammation-induced muscle atrophy.2022

    • Author(s)
      Atomu Yamaguchi, Yuichi Nishida, Noriaki Maeshige, Maiki Moriguchi, Mikiko Uemura, Xiaoqi Ma, Makoto Miyoshi, Hiroyo Kondo, Hidemi Fujino.
    • Organizer
      39th Congress of the International Union of Physiological Sciences
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Niacin supplementation attenuates capillary regression and oxidative phosphorylation enzyme depletion in unloaded rat skeletal muscle2022

    • Author(s)
      Hao LIN, Hao Ji XING, Han PAN, Takumi HIRABAYASHI, Noriaki MASHIGE, Hiroyo KONDO, Hidemi FUJINO
    • Organizer
      39th Congress of the International Union of Physiological Sciences
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 健康な若年女性における軽度高気圧酸素の末梢血単核細胞に対する効果2022

    • Author(s)
      Badur Un Nisa, 天野英紀,藤澤秋子, 平林卓巳, 近藤浩代,藤野英己
    • Organizer
      第77回日本体力医学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 低圧低酸素環境により誘導される血管新生因子の発現と骨格筋損傷の治癒促進の効果2022

    • Author(s)
      天野英紀,藤澤秋子,中山慧美,Badur Un Nisa,近藤浩代,藤野 英己
    • Organizer
      第77回日本体力医学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] アンギオテンシンⅠ転換酵素の遺伝子多型が低圧低酸素環境における酸素飽和度に及ぼす影響2022

    • Author(s)
      藤澤秋子,天野英紀,Badur Un Nisa,Lin Hao, Dong Yi, 近藤浩代,藤野英己
    • Organizer
      第77回日本体力医学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 低栄養状態の骨格筋に対する中鎖脂肪酸トリグリセリド摂取の効果2022

    • Author(s)
      平林卓己,Jihao Xing,前重伯壮,近藤浩代,藤野英己
    • Organizer
      第31回日本脂質栄養学会大
    • Related Report
      2021 Annual Research Report
  • [Presentation] 骨格筋におけるマイオカインIL-15がオートファジー機構に及ぼす影響2022

    • Author(s)
      田中稔,杉本研, 高橋利匡,赤坂憲,山本浩一, 藤野英己,樂木宏実
    • Organizer
      第27回日本基礎理学療法学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 培養筋管由来細胞外小胞によるイタコン酸産生を介したマクロファージ炎症反応抑制2022

    • Author(s)
      山口亜斗夢, 前重伯壮, 植村弥希子, Ma Xiaoqi, 寺師浩人, 近藤 浩代, 藤野英己
    • Organizer
      第52回日本創傷治癒学会学術大会
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Presentation] 直流微弱電流はマクロファージ内グリコーゲン分解およびペントースリン酸経路の賦活を介して抗酸化・抗炎症作用を発揮する2022

    • Author(s)
      植村弥希子, 前重伯壮, 山口亜斗夢, Ma Xiaoqi, 井上岳人, 寺師浩人, 近藤 浩代, 藤野, 英己
    • Organizer
      第52回日本創傷治癒学会学術大会
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Presentation] 低パルス繰り返し周波数での超音波照射が培養筋管からの細胞外小胞放出に与える促進効果2022

    • Author(s)
      谷田健斗, Xiaoqi Ma, 山口亜斗夢, 前重伯壮, 植村弥希子, 近藤浩代, 藤野英己
    • Organizer
      第 77 回 日本体力医学会
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Presentation] 骨格筋の毛細血管退行に対する核酸の抗酸化作用及び血管内皮細胞増殖因子の発現による予防効果2022

    • Author(s)
      橋本渚,宅和美穂,中西亮介,植村弥希子,藤野英己
    • Organizer
      第 77 回 日本体力医学会
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 骨格筋内オートファジー制御に筋由来IL-15が及ぼす効果2022

    • Author(s)
      田中稔,赤坂憲,杉本研, 高橋利匡,山本浩一, 藤野英己,樂木宏実
    • Organizer
      第 77 回 日本体力医学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Niacin supplementation attenuates capillary regression and oxidative phosphorylation enzyme depletion in unloaded rat skeletal muscle2022

    • Author(s)
      Hao LIN , Han PAN, Jihao XING, Takumi HIRABAYASHI, Noriaki MASHIGE, Hiroyo KONDO, Hidemi FUJINO
    • Organizer
      22nd IUNS-ICN
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Green coffee bean extract protects muscle capillary regression via decreased oxidative stress under disuse condition.2022

    • Author(s)
      Jihao Xing, Han Pan, Hao Lin, Ryosuke Nakanishi, Takumi Hirabayashi, Xiaoqi Ma, Kazuya Iwai, Noriaki Maeshige, Hiroyo Kondo, Hidemi Fujino
    • Organizer
      22nd IUNS-ICN
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 超音波照射はマクロファージ内のイタコン酸産生を促進して過剰炎症反応を抑制する2022

    • Author(s)
      山口亜斗夢, 前重伯壮, 馬暁_, 植村弥希子, 野口ひかり, 近藤浩代, 藤野英己
    • Organizer
      日本物理療法合同学術大会
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Presentation] 骨格筋内オートファジーにマイオカインIL-15が及ぼす効果2022

    • Author(s)
      田中稔,赤坂憲,杉本研, 高橋利匡,山本浩一, 藤野英己,樂木宏実
    • Organizer
      第33回日本老年医学会近畿地方会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 電気刺激はマクロファージのHIF-1αを抑制し細胞内代謝を変化させることで抗炎症・抗酸化作用を発揮する2022

    • Author(s)
      植村弥希子, 前重伯壮, 山口亜斗夢, Ma Xiaoqi, 井上岳人, 近藤浩代, 藤野英己
    • Organizer
      日本物理療法合同学術大会
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Presentation] 筋由来IL-15が骨格筋内オートファジー制御に及ぼす効果2022

    • Author(s)
      田中 稔, 杉本 研, 赤坂 憲, 高橋 利匡, 山本 浩一, 藤野 英己, 樂木 宏実
    • Organizer
      第8回日本筋学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Conditioned Media from Ultrasound treated C2C12 Myotubes Regulate Macrophage Inflammatory Responses.2021

    • Author(s)
      Yamaguchi A, Maeshige N, Langston PK, Noguchi H, Ma X, Ichikawa Y, Uemura M, Kondo H, Fujino H.
    • Organizer
      Experimental Biology
    • Related Report
      2019 Annual Research Report
  • [Presentation] Effect of high intensity ultrasound irradiation on exosomes release from cultured myotubes.2021

    • Author(s)
      Noguchi H, Maeshige N, Langston PK, Yamaguchi A, Uemura M, Nakanishi R, Kondo H, Fujino H.
    • Organizer
      Experimental Biology
    • Related Report
      2019 Annual Research Report
  • [Presentation] 電気刺激による筋収縮の骨格筋由来エクソソーム放出促進の効果.2021

    • Author(s)
      市川祐介, 山口亜斗夢, 野口ひかり, Ma X, 近藤浩代, 前重伯壮, 藤野英己.
    • Organizer
      第26回日本基礎理学療法学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 高強度超音波照射が培養筋管由来の細胞外小胞放出に与える効果2020

    • Author(s)
      野口ひかり,中山慧美,林浩,Bardur Un Nisa Safdar, 平林卓己,植村弥希子,中西亮介,田中稔,近藤浩代,前重伯壮,藤野英己
    • Organizer
      第110回理学療法科学学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 超音波照射による細胞内カルシウム濃度上昇が骨格筋由来エクソソーム放出に与える効果2020

    • Author(s)
      野口ひかり, 中山慧美,平林卓己,近藤浩代,前重伯壮,藤野英己
    • Organizer
      第75回日本体力医学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Amelioration of Diabetes-associated Muscle Atrophy by Transcutaneous Carbon Dioxide Exposure.2019

    • Author(s)
      Kondo H, Fujino H, Matsumoto T, Ishihara A.
    • Organizer
      6th Annual Meeting of the American College of Sports Medicine
    • Related Report
      2019 Annual Research Report

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Published: 2019-04-18   Modified: 2024-01-30  

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