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Elucidation of Extracellular Vesicles Contributing Liver and Muscle Linkage

Research Project

Project/Area Number 20K08326
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionNiigata University

Principal Investigator

Kamimura Hiroteru  新潟大学, 医歯学総合病院, 講師 (40706420)

Co-Investigator(Kenkyū-buntansha) 寺井 崇二  新潟大学, 医歯学系, 教授 (00332809)
土屋 淳紀  新潟大学, 医歯学総合病院, 講師 (70464005)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords肝硬変 / サルコペニア / 老化 / 肝筋相関 / エクソソーム / サルコぺニア / 肝性脳症 / SLC6A9 / GlyT1 / マイオカイン / オープンフィールド / 細胞外小胞 / miRNA
Outline of Research at the Start

高齢化が進む我が国において、加齢に伴い医療・介護費を増加させる病態であるサルコペニア(筋肉の量・機能低下)への対策は喫緊の課題である。肝不全では早期にサルコペニアが出現する事が注目されているが、本研究ではその病態を解明するためのモデル動物の作成、早期の段階で介入の指標となるバイオマーカーの確立を目指す。
肝不全サルコペニアモデルや臨床検体からプロテオミクス、miRNA解析を行い、モデル動物の結果と照合し、肝不全時に筋肉を臓器不全へ陥らせるサルコペニアのEVバイオマーカーを確立し、次世代型サルコペニア対策へと結び付ける。

Outline of Final Research Achievements

We searched for markers of early detection associated with sarcopenia in a mouse model of liver cirrhosis. Since it had been reported that spontaneous locomotion using a rotating cage suppressed hepatic carcinogenesis, we measured changes in liver tissue, fibrosis markers, muscle strength, muscle tissue, myokine, and extracellular vesicles over a short period of time using a rotating cage spontaneous locomotion measuring device in a cirrhotic mouse model. For myokine, multiplex assay analysis was performed on serum and direct muscle to identify key factors in the inter-organ system that contribute to the improvement of liver function by rehabilitation. We aim to identify key factors involved in the organ systems that contribute to the improvement of liver function by exercise rehabilitation.

Academic Significance and Societal Importance of the Research Achievements

肝硬変はB型肝炎、C型肝炎、脂肪肝、アルコール摂取などが主な原因で長期に肝臓が障害を受け、徐々に線維化が進み、非代償性肝硬変(黄疸、腹水、肝性脳症)になる。また長期的には肝細胞癌などを来す致死的な疾患で、日本に患者さんは40万人程度存在する。また肝硬変患者の高齢化もすすんできて、10-70%がサルコペニアを合併している。本研究結果をもとに、学会内でのリハビリテーション委員会を立ち上げ、市民公開講座開催予定して、臨床的還元を狙っている。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (30 results)

All 2023 2022 2021 2020

All Journal Article (23 results) (of which Peer Reviewed: 18 results,  Open Access: 8 results) Presentation (5 results) Book (2 results)

  • [Journal Article] Liver disease and sarcopenia:the future of rehabilitation medicine -it has to be fun to keep going-2023

    • Author(s)
      寺井 崇二、上村 博輝
    • Journal Title

      Nippon Shokakibyo Gakkai Zasshi

      Volume: 120 Issue: 9 Pages: 701-708

    • DOI

      10.11405/nisshoshi.120.701

    • ISSN
      0446-6586, 1349-7693
    • Year and Date
      2023-09-10
    • Related Report
      2023 Annual Research Report
  • [Journal Article] Complementary role of peripheral and central autonomic nervous system on insulin-like growth factor-1 activation to prevent fatty liver disease2023

    • Author(s)
      Nagayama Itsuo、Kamimura Kenya、Owaki Takashi、Ko Masayoshi、Nagoya Takuro、Tanaka Yuto、Ohkoshi Marina、Setsu Toru、Sakamaki Akira、Yokoo Takeshi、Kamimura Hiroteru、Terai Shuji
    • Journal Title

      Hepatology International

      Volume: 18 Issue: 1 Pages: 155-167

    • DOI

      10.1007/s12072-023-10601-1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of drug‐induced liver‐related adverse event trend reporting between 1997 and 20192023

    • Author(s)
      Kamimura Hiroteru、Setsu Toru、Kimura Naruhiro、Miyazawa Makoto、Kaneko Shota、Kamimura Kenya、Tsuchiya Atsunori、Uesawa Yoshihiro、Terai Shuji
    • Journal Title

      Hepatology Research

      Volume: in press Issue: 6 Pages: 556-568

    • DOI

      10.1111/hepr.13883

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Navitoclax improves acute‐on‐chronic liver failure by eliminating senescent cells in mice2023

    • Author(s)
      Watanabe Yusuke、Abe Hiroyuki、Kimura Naruhiro、Arao Yoshihisa、Ishikawa Natsuki、Yuichiro Maeda、Setsu Toru、Sakamaki Akira、Kamimura Hiroteru、Yokoo Takeshi、Kamimura Kenya、Tsuchiya Atsunori、Terai Shuji
    • Journal Title

      Hepatology Research

      Volume: 53 Issue: 5 Pages: 460-472

    • DOI

      10.1111/hepr.13879

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] HBx and YAP expression could promote tumor development and progression in HBV-related hepatocellular carcinoma2022

    • Author(s)
      Oda Chiyumi、Kamimura Kenya、Shibata Osamu、Morita Shinichi、Tanaka Yuto、Setsu Toru、Abe Hiroyuki、Yokoo Takeshi、Sakamaki Akira、Kamimura Hiroteru、Kofuji Satoshi、Wakai Toshifumi、Nishina Hiroshi、Terai Shuji
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 32 Pages: 101352-101352

    • DOI

      10.1016/j.bbrep.2022.101352

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Letrozole ameliorates liver fibrosis through the inhibition of the CTGF pathway and 17β-hydroxysteroid dehydrogenase 13 expression2022

    • Author(s)
      Sakai Norihiro、Kamimura Kenya、Miyamoto Hirotaka、Ko Masayoshi、Nagoya Takuro、Setsu Toru、Sakamaki Akira、Yokoo Takeshi、Kamimura Hiroteru、Soki Hiroyuki、Tokunaga Ayako、Inamine Tatsuo、Nakashima Mikiro、Enomoto Hatsune、Kousaka Kazuki、Tachiki Hidehisa、Ohyama Kaname、Terai Shuji
    • Journal Title

      Journal of Gastroenterology

      Volume: 58 Issue: 1 Pages: 53-68

    • DOI

      10.1007/s00535-022-01929-w

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of a selective PPARα modulator, sodium-glucose cotransporter 2 inhibitor, and statin on the myocardial morphology of medaka nonalcoholic fatty liver disease model2022

    • Author(s)
      Ohkoshi-Yamada Marina、Kamimura Kenya、Kimura Atsushi、Tanaka Yuto、Nagayama Itsuo、Yakubo Shunta、Abe Hiroyuki、Yokoo Takeshi、Sakamaki Akira、Kamimura Hiroteru、Terai Shuji
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 625 Pages: 116-121

    • DOI

      10.1016/j.bbrc.2022.07.117

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of the liver-gut peripheral neural axis in nonalcoholic fatty liver disease pathologies via hepatic HTR2A2022

    • Author(s)
      Owaki Takashi、Kamimura Kenya、Ko Masayoshi、Nagayama Itsuo、Nagoya Takuro、Shibata Osamu、Oda Chiyumi、Morita Shinichi、Kimura Atsushi、Sato Takeki、Setsu Toru、Sakamaki Akira、Kamimura Hiroteru、Yokoo Takeshi、Terai Shuji
    • Journal Title

      Disease Models & Mechanisms

      Volume: 15 Issue: 7

    • DOI

      10.1242/dmm.049612

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of DNA Damage Response via the Ccndbp1-Atm-Chk2 Pathway in Mice with Dextran-Sodium-Sulfate-Induced Colitis2022

    • Author(s)
      Horigome R, Kamimura K, Niwa Y, Ogawa K, Mizuno KI, Fujisawa K, Yamamoto N, Takami T, Sugano T, Sakamaki A, Kamimura H, Takamura M, Terai S.
    • Journal Title

      J Clin Med.

      Volume: 11(13) Issue: 13 Pages: 3674-3680

    • DOI

      10.3390/jcm11133674

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cyclin D1 Binding Protein 1 Responds to DNA Damage through the ATM / CHK2 Pathway2022

    • Author(s)
      Niwa Yusuke、Kamimura Kenya、Ogawa K、Oda C、Tanaka Y、Horigome R、Ohtsuka M、Miura H、Fujisawa Koichi、Yamamoto Naoki、Takami Taro、Okuda Shujiro、Ko Masayoshi、Owaki Takashi、Kimura Atsushi、Shibata Osamu、Morita Shinichi、Sakai N、Abe H、Yokoo T、Sakamaki A、Kamimura H、Terai S
    • Journal Title

      Journal of Clinical Medicine

      Volume: 11 Issue: 3 Pages: 851-851

    • DOI

      10.3390/jcm11030851

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Use of a Deep Learning Approach for the Sensitive Prediction of Hepatitis B Surface Antigen Levels in Inactive Carrier Patients2022

    • Author(s)
      Kamimura Hiroteru、Nonaka Hirofumi、Mori Masaya、Kobayashi Taichi、Setsu Toru、Kamimura Kenya、Tsuchiya Atsunori、Terai Shuji
    • Journal Title

      Journal of Clinical Medicine

      Volume: 11 Issue: 2 Pages: 387-387

    • DOI

      10.3390/jcm11020387

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Potential Effect of a Selective Peroxisome Proliferator-activated Receptor Alpha Modulator on Metabolic Dysfunction-associated Fatty Liver Disease2021

    • Author(s)
      Kamimura Hiroteru、Kimura Atsushi、Terai Shuji
    • Journal Title

      Internal Medicine

      Volume: 60 Issue: 14 Pages: 2165-2166

    • DOI

      10.2169/internalmedicine.6906-20

    • NAID

      130008065147

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2021-07-15
    • Related Report
      2021 Research-status Report 2020 Research-status Report
  • [Journal Article] Rare complication of hepatocellular carcinoma in Wilson's disease2021

    • Author(s)
      Ohkoshi‐Yamada Marina、Kamimura Kenya、Kamimura Hiroteru、Terai Shuji
    • Journal Title

      JGH Open

      Volume: 5 Issue: 10 Pages: 1220-1222

    • DOI

      10.1002/jgh3.12648

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesized HMGB1 peptide attenuates liver inflammation and suppresses fibrosis in mice.2021

    • Author(s)
      Nojiri S, Tsuchiya A, Natsui K, Takeuchi S, Watanabe T, Kojima Y, Watanabe Y, Kamimura H, Ogawa M, Motegi S, Iwasawa T, Sato T, Kumagai M, Ishii Y, Kitayama T, Li YT, Ouchi Y, Shimbo T, Takamura M, Tamai K, Terai S
    • Journal Title

      Inflamm Regen

      Volume: 41(1) Issue: 1 Pages: 28-28

    • DOI

      10.1186/s41232-021-00177-4

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rapid Onset of Weight Gain and Liver Dysfunction Successfully Treated With Nutrition and Exercise2021

    • Author(s)
      Kamimura Hiroteru、Sano Masakazu、Tsujimura Takanori、Takeda Yasunaga、Komoro Yuko、Yokoyama Junji、Terai Shuji
    • Journal Title

      Cureus

      Volume: 22 Pages: 0-11

    • DOI

      10.7759/cureus.16530

    • Related Report
      2021 Research-status Report
  • [Journal Article] The prognosis and incidence of hepatic encephalopathy of patients with liver cirrhosis treated with proton pump inhibitors2021

    • Author(s)
      Sakamaki Akira、Kamimura Kenya、Yokoo Takeshi、Osaki Akihiko、Yoshikawa Seiichi、Arao Yoshihisa、Setsu Toru、Kamimura Hiroteru、Waguri Nobuo、Takeuchi Manabu、Funakoshi Kazuhiro、Terai Shuji
    • Journal Title

      Medicine

      Volume: 100 Issue: 32 Pages: e26902-e26902

    • DOI

      10.1097/md.0000000000026902

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Severe steatosis and mild colitis are important for the early occurrence of hepatocellular carcinoma2021

    • Author(s)
      Sato Takeki、Tsuchiya Atsunori、Owaki Takashi、Kumagai Masaru、Motegi Satoko、Iwasawa Takahiro、Nojiri Shunsuke、Ogawa Masahiro、Takeuchi Suguru、Watanabe Yusuke、Kawata Yuzo、Kamimura Hiroteru、Terai Shuji
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 566 Pages: 36-44

    • DOI

      10.1016/j.bbrc.2021.05.097

    • Related Report
      2021 Research-status Report
  • [Journal Article] Paris II and Rotterdam criteria are the best predictors of outcomes in patients with primary biliary cholangitis in Japan2021

    • Author(s)
      Kimura N, Takamura M, Takeda N, Watanabe Y, Arao Y, Takatsuna M, Takeuchi S, Abe H, Setsu T, Kamimura H, Sakamaki A, Kamimura K, Tsuchiya A, and Terai S.
    • Journal Title

      Hepatology International

      Volume: 15 Issue: 2 Pages: 437-443

    • DOI

      10.1007/s12072-021-10163-0

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Successful treatment of positive-sense RNA virus coinfection with autoimmune hepatitis using double filtration plasmapheresis2021

    • Author(s)
      Kamimura Hiroteru、Kamimura Kenya、Tsuchiya Atsunori、Terai Shuji
    • Journal Title

      BMJ Case Reports

      Volume: 14 Issue: 3 Pages: e236984-e236984

    • DOI

      10.1136/bcr-2020-236984

    • Related Report
      2021 Research-status Report 2020 Research-status Report
  • [Journal Article] Relationship between detection of hepatitis B virus in saliva and periodontal disease in hepatitis B virus carriers in Japan, Journal of Infection and Chemotherapy2021

    • Author(s)
      Kamimura Hiroteru, Jun Watanabe, Tomoyuki Sugano, Junji Kohisa, Hiroyuki Abe, Keny Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Shogo Okoshi, Yoshinari Tanabe, Ritsuo Takagi, Hirofumi Nonaka, Shuji Terai
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: Vol.27, No.3 Issue: 3 Pages: 492-496

    • DOI

      10.1016/j.jiac.2020.10.028

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular Mechanisms and Treatment of Sarcopenia in Liver Disease: A Review of Current Knowledge2021

    • Author(s)
      Kamimura Hiroteru、Sato Takeki、Natsui Kazuki、Kobayashi Takamasa、Yoshida Tomoaki、Kamimura Kenya、Tsuchiya Atsunori、Murayama Toshiko、Yokoyama Junji、Kawai Hirokazu、Takamura Masaaki、Terai Shuji
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 3 Pages: 1425-1425

    • DOI

      10.3390/ijms22031425

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ten years' experience in Niigata Prefecture Liver Disease Consultation Center2020

    • Author(s)
      Kamimura Hiroteru、Setsu Toru、Arao Yoshihisa、Hirokawa Hikaru、Sawaguri Hiromi、Watanabe Fumiko、Komoro Yuko、Sakamaki Akira、Tsuchiya Atsunori、Takamura Masaaki、Ikarashi Masato、Aoyagi Yutaka、Kikuta Rei、Watanabe Kazuhito、Nakayama Hitoshi、Tamura Tsutomu、Terai Shuji
    • Journal Title

      Kanzo

      Volume: 61 Issue: 5 Pages: 245-254

    • DOI

      10.2957/kanzo.61.245

    • NAID

      130007841505

    • ISSN
      0451-4203, 1881-3593
    • Year and Date
      2020-05-01
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Monitoring chronological change by liver-to-spleen attenuation ratio for secondary hepatic steatosis for a short term2020

    • Author(s)
      Kamimura Hiroteru、Yokoyama Kunihiko、Nojiri Shunsuke、Komoro Yuko、Murayama Toshiko、Koyama Yu、Kamimura Kenya、Takamura Masaaki、Yokoyama Junji、Terai Shuji
    • Journal Title

      Clinical Journal of Gastroenterology

      Volume: 13 Issue: 6 Pages: 1219-1224

    • DOI

      10.1007/s12328-020-01165-w

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] 門脈圧亢進症と臓器相関 心、肝、肺、腎、脾 当院における心不全に伴う肝臓への影響(Cardiac Hepatopathy)の解析2022

    • Author(s)
      上村 博輝, 寺井 崇二, 猪又 孝文, 三井田 秀, 山崎 文紗子, 柏村 健, 藤木 信也, 渡邊 雄介, 荒生 祥尚, 木村 成宏, 阿部 寛幸, 薛 徹, 坂牧 僚, 横尾 健
    • Organizer
      日本門脈圧亢進症学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 肝疾患の小児・成人移行期医療の課題-全人的ケアの確立を目指して 成人外来へ受診する可能性をもつ小児脂肪肝の特徴2022

    • Author(s)
      上村博輝 上村顕也 寺井崇二
    • Organizer
      日本肝臓学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 門脈圧亢進症と臓器相関 心、肝、肺、腎、脾 当院における心不全に伴う肝臓への影響(Cardiac Hepatopathy)の解析2021

    • Author(s)
      上村 博輝, 寺井 崇二, 猪又 孝文, 三井田 秀, 山崎 文紗子, 柏村 健, 藤木 信也, 渡邊 雄介, 荒生 祥尚, 木村 成宏, 阿部 寛幸, 薛 徹, 坂牧 僚, 横尾 健
    • Organizer
      日本門脈圧亢進症学会雑誌 27(3) 109-109 2021年8月
    • Related Report
      2021 Research-status Report
  • [Presentation] 併存する疾患のあることが多い高齢者における上部消化管疾患のマネージメント 地域病院における消化器サルコペニア疾患診療の有用性2021

    • Author(s)
      上村 博輝, 小島 雄一, 高橋 一也, 高綱 将史, 平野 正明, 政二 文明, 藤田 一, 辻村 恭憲, 小林 太一, 寺井 崇二
    • Organizer
      日本消化器病学会甲信越支部例会抄録集 68回 52-52 2021年6月
    • Related Report
      2021 Research-status Report
  • [Presentation] 肝疾患におけるビックデータとAI(人工知能)の臨床応用 ディープラーニングを活用したPBC多施設データから予測する高齢者PBCの介入の必要性の検討2021

    • Author(s)
      上村 博輝, 高村 昌昭, 寺井 崇二
    • Organizer
      肝臓 62(Suppl.1) A208-A208 2021年4月
    • Related Report
      2021 Research-status Report
  • [Book] 【肝疾患エキスパートブック 栄養管理に活かすための最新情報】(Part 1)肝硬変 肝硬変に対する運動療法につい2021

    • Author(s)
      上村 博輝, 寺井 崇二, 眞田 菜緒, 小師 優子
    • Total Pages
      6
    • Publisher
      医歯薬出版(株)
    • Related Report
      2021 Research-status Report
  • [Book] 小児期発症慢性肝疾患における移行期医療の現状と課題-小児と成人のダイアログ-】NAFLD Pediatric fatty liver disease(PeFLD)における概説と成人との比較(肝組織学的検討を含めて) 小児と成人の相違2021

    • Author(s)
      上村 博輝, 山崎 文紗子, 佐藤 毅昂, 薛 徹, 土屋 淳紀, 上村 顕也, 高村 昌昭, 寺井 崇二, 長崎 啓祐, 斎藤 昭彦, 梅津 哉
    • Total Pages
      15
    • Publisher
      (株)アークメディア
    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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