津川 仁 (ツガワ ヒトシ)

Tsugawa, Hitoshi

写真a

所属(所属キャンパス)

医学部 医化学教室 (信濃町)

職名

専任講師(有期)

メールアドレス

メールアドレス

学位 【 表示 / 非表示

  • 博士(薬学), 東北薬科大学大学院 薬学研究科

免許・資格 【 表示 / 非表示

  • 薬剤師

 

研究分野 【 表示 / 非表示

  • 医化学一般

  • 細菌学(含真菌学)

 

著書 【 表示 / 非表示

  • H. pylori感染症を制御する病原因子と宿主細胞応答

    津川 仁, 鈴木秀和, 日本防菌防黴学会誌, 2018年

  • H. pylori感染症と宿主免疫応答.

    津川 仁, 鈴木秀和, 臨床と微生物, 2015年

  • Helicobacter pylori感染とオートファジー

    鈴木 秀和, 津川 仁, G.I.Reserch, 2015年

  • H. pyloriがん蛋白質CagAのCD44v9発現がん幹細胞特異的蓄積メカニズムの発見-細胞内CagA安定性を規定する細胞表層LRP1のautophagy制御機構-

    津川 仁, 日本ヘリコバクター学会誌, 2014年

  • ピロリ菌の感染戦略と胃がん発症に関わる宿主応答機構の解析

    津川 仁, 日本細菌学雑誌, 2014年

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論文 【 表示 / 非表示

  • CAPZA1 determines the risk of gastric carcinogenesis by inhibiting Helicobacter pylori CagA-degraded autophagy

    Tsugawa H., Mori H., Matsuzaki J., Sato A., Saito Y., Imoto M., Suematsu M., Suzuki H.

    Autophagy (Autophagy)  15 ( 2 ) 242 - 258 2019年02月

    ISSN  15548627

     概要を見る

    © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group. Helicobacter pylori-derived CagA, a type IV secretion system effector, plays a role as an oncogenic driver in gastric epithelial cells. However, upon delivery into gastric epithelial cells, CagA is usually degraded by macroautophagy/autophagy. Hence, the induction of autophagy in H. pylori-infected epithelial cells is an important host-protective ability against gastric carcinogenesis. However, the mechanisms by which autophagosome-lysosome fusion is regulated, are unknown. Here, we report that enhancement of LAMP1 (lysosomal associated membrane protein 1) expression is necessary for autolysosome formation. LAMP1 expression is induced by nuclear translocated LRP1 (LDL receptor related protein 1) intracellular domain (LRP1-ICD) binding to the proximal LAMP1 promoter region. Nuclear translocation of LRP1-ICD is enhanced by H. pylori infection. In contrast, CAPZA1 (capping actin protein of muscle Z-line alpha subunit 1) inhibits LAMP1 expression via binding to LRP1-ICD in the nuclei. The binding of CAPZA1 to LRP1-ICD prevents LRP1-ICD binding to the LAMP1 proximal promoter. Thus, in CAPZA1-overexpressing gastric epithelial cells infected with H. pylori, autolysosome formation is inhibited and CagA escapes autophagic degradation. These findings identify CAPZA1 as a novel negative regulator of autolysosome formation and suggest that deregulation of CAPZA1 expression leads to increased risk of gastric carcinogenesis. Abbreviations: CagA: cytotoxin-associated gene A; CAPZA1: capping actin protein of muscle Z-line alpha subunit 1; ChIP: chromatin immunoprecipitation; GTF2I: general transcription factor IIi; HDAC: histone deacetylase; LAMP1: lysosomal associated membrane protein 1; LRP1: LDL receptor related protein 1; LRP1-ICD: CagA intracellular domain; qPCR: quantitative polymerase chain reaction; VacA: vacuolating cytotoxin.

  • Neutrophil-activating Protein Polymorphism of Helicobacter pylori Determines the Host Risk of Dyspepsia

    Matsuzaki J., Tsugawa H., Kashiwazaki Y., Mori H., Yamamoto Y., Kameyama H., Masaoka T., Kanai T., Suzuki H.

    Cellular and Molecular Gastroenterology and Hepatology (Cellular and Molecular Gastroenterology and Hepatology)  8 ( 2 ) 295 - 297.e6 2019年

  • Cancer Stem-Cell Marker CD44v9-Positive Cells Arise From Helicobacter pylori–Infected CAPZA1-Overexpressing Cells

    Tsugawa H., Kato C., Mori H., Matsuzaki J., Kameyama K., Saya H., Hatakeyama M., Suematsu M., Suzuki H.

    Cellular and Molecular Gastroenterology and Hepatology (Cellular and Molecular Gastroenterology and Hepatology)  8 ( 3 ) 319 - 334 2019年

     概要を見る

    © 2019 The Authors Background & Aims: CD44 variant 9 (CD44v9)-positive cancer stem-like cells strongly contribute to the development and recurrence of gastric cancer. However, the origin of CD44v9-positive cells is uncertain. Methods: CD44v9, β-catenin, and epithelial splicing regulatory protein 1 signals were assessed by real-time reverse-transcription polymerase chain reaction, immunoblot analysis, or immunofluorescence microscopy. Capping actin protein of muscle Z-line α subunit 1 (CAPZA1) expression was assessed by immunoblot analysis or immunohistochemical analysis of Mongolian gerbils' gastric mucosa or human biopsy specimens. Levels of oxidative stress were assessed by measuring malondialdehyde and protein carbonylation. Histone H3 acetylation levels in the CAPZA1 proximal promoter region were measured by using chromatin immunoprecipitation analysis with an antibody against the acetylated histone H3 in human gastric carcinoma cell line (AGS) cells. Results: CD44v9 is expressed in CAPZA1-overexpressing cells in human gastric cancer tissues. CAPZA1 overexpression enhanced expression of β-catenin, which is a transcription factor for CD44, and epithelial splicing regulatory protein 1, which increases alternative splicing of CD44 to generate CD44v9. CAPZA1-overexpressing cells after cytotoxin-associated gene A accumulation showed CD44v9 expression by inducing nuclear accumulation of β-catenin, concomitant with the enhancement of expression of Sal-like protein 4 and Krüppel-like factor 5, which encode reprogramming factors. Oxidative stress increased the CAPZA1 expression in AGS cells through the enhancement of histone H3 acetylation of CAPZA1 promoter. CAPZA1 expression was increased depending on oxidative stress in H pylori–infected gastric mucosa. Conclusions: CD44v9 expression is evoked from CAPZA1-overexpressing cells after accumulation of cytotoxin-associated gene A. Our findings provide important insights into the mechanisms underlying the development of CD44v9-positive cells.

  • Inhibiting xCT improves 5-fluorouracil resistance of gastric cancer induced by CD44 variant 9 expression

    Miyoshi S., Tsugawa H., Matsuzaki J., Hirata K., Mori H., Saya H., Kanai T., Suzuki H.

    Anticancer Research (Anticancer Research)  38 ( 11 ) 6163 - 6170 2018年11月

    ISSN  02507005

     概要を見る

    © 2018 International Institute of Anticancer Research.All right reserved. Background/Aim: Cancer stem cells (CSCs) play a critical role in resistance to chemotherapy. CD44 is a cell surface marker of CSCs. CD44 variant 9 (CD44v9) interacts with a cystine-glutamate antiporter (xCT) and is an unfavorable predictive factor in gastric cancer. We investigated the impact of CD44v9 expression on 5-fluorouracil (5-FU) resistance and the efficacy of the xCT inhibitor, sulfasalazine (SASP), in improving drug resistance. Materials and Methods: The human gastric cancer cell line MKN28 was transfected with pRc/CMV plasmids encoding human CD44 or CD44v9, which were used for in vitro and in vivo experiments. Results: CD44v9 expression results in 5-FU resistance by increasing intracellular glutathione and suppressing the drug-induced production of reactive oxygen species (ROS). SASP improved the drug sensitivity of CD44v9-expressing cells. Conclusion: Inhibition of xCT improved the clinical efficacy of chemotherapy against gastric cancer. CD44v9 expression can be a novel biomarker to predict resistance against 5-FU in gastric cancer.

  • CAPZA1 determines the risk of gastric carcinogenesis by inhibiting Helicobcater pylori CagA-degraded autophagy.

    Tsugawa H., Mori H., Matsuzaki J., Sato A., Saito Y., Imoto M., Suematsu M., Suzuki H.

    Autophagy Epub ahead of print 2018年

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

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研究発表 【 表示 / 非表示

  • 宿主細胞内へ装填されたピロリ菌がん蛋白質CagAの安定性を規定する宿主細胞分子とその制御

    津川 仁、加藤智尋、森英毅、松崎潤太郎、佐藤聡、斉藤義正、末松誠、 鈴木秀和

    第65回トキシンシンポジウム, 2018年, 口頭(一般)

  • Overexpression of CAPZA1, a novel negative regulator of autophagy, develops CD44v9-expressing cancer stem-like cells in Helicobacter pylori-infected gastric mucosa

    Tsugawa H., Matsuzaki J., Kato C., Mori H., Suematsu M., Suzuki H.

    XXXIst International Workshop on Helicobacter & Microbiota in Inflammation & Cancer, 2018年, ポスター(一般)

  • Mechanisms of CD44v9-positive cancer stem cell development in H. pylori-infected gastric mucosa

    Tsugawa H.

    The 17th Awaji International Forum on Infection and Immunity, 2018年, 口頭(招待・特別)

  • Association between oxidative stress and gastric carcinogenesis in H. pylori-infected patients

    Tsugawa H., Kato C., Mori H., Suematsu M., Suzuki H.

    Summer School on Stress 2018, 2018年, 口頭(招待・特別)

  • Expression of CAPZA1, a negative regulator of CagA-degrading autophagy, is enhanced by oxidative stress-induced histone acetylation in Helicobacter pylori-infected gastric mucosa: A possible risk for gastric carcinogenesis

    Kato C., Tsugawa H., Saito Y., Suzuki H.

    Digestive Disease Week 2018, 2018年, 口頭(一般)

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競争的資金等の研究課題 【 表示 / 非表示

  • H. pylori感染と消化管内共生細菌との連動による胃癌幹細胞発生機序の解析

    2019年04月
    -
    2022年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 津川 仁, 基盤研究(C), 補助金,  代表

  • 胃発がんリスク亢進に繋がるピロリ菌感染宿主細胞の分子特性解析

    2016年04月
    -
    2019年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 津川 仁, 基盤研究(C), 補助金,  代表

受賞 【 表示 / 非表示

  • 第21回 日本ヘリコバクター学会 上原H. pylori優秀賞

    2015年

    受賞区分: 国内学会・会議・シンポジウム等の賞

  • 日本細菌学会黒屋奨学賞

    2014年03月, 日本細菌学会

  • 日本細菌学会黒屋奨学賞

    2014年

    受賞区分: 国内学会・会議・シンポジウム等の賞

  • The 6th International Gastrointestinal Consensus Symposium (IGICS) Gold Medal Award

    2013年

    受賞区分: 国内外の国際的学術賞

  • 第19回 日本ヘリコバクター学会 上原H. pylori賞~最優秀賞~

    2013年

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担当授業科目 【 表示 / 非表示

  • 医化学

    2019年度

 

所属学協会 【 表示 / 非表示

  • 日本細菌学会

     
  • 日本薬学会

     
  • 日本ヘリコバクター学会

     
  • 日本分子生物学会

     
  • 日本癌学会

     

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委員歴 【 表示 / 非表示

  • 2016年
    -
    継続中

    評議員, 日本ヘリコバクター学会

  • 2017年
    -
    継続中

    学会賞選考委員, 日本ヘリコバクター学会