Studies on upregulated or downregulated genes depending on cardiac hypertrophy

• Project/Area Number: 19K11730
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Kindai University
• Principal Investigator: MAENISHI Osamu 近畿大学, 医学部, 講師 (20298946)
• Co-Investigator(Kenkyū-buntansha): 井上 敬夫 近畿大学, 医学部, 助教 (00441006)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 心肥大 / 高血圧 / 心肥大関連タンパク質 / 心肥大抑制

Outline of Research at the Start

新規に見出した心肥大関連タンパク質群に関して心肥大発症過程においてどのような発現パターンがみられるのか解析する。これらのタンパク質の中から特に心肥大との強い関連性が示唆されるものに関して、機能解析及び心肥大と関連するメカニズムについての解明を行う。最終的には心肥大関連タンパク質を標的とした化合物のスクリーニングを行い、治療薬開発への足掛かりとする。

Outline of Final Research Achievements

Spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP) show different cardiac hypertrophy compared to normotensive rats, Wistar-Kyoto rats (WKY). Comprehensive gene expression analysis for left ventricular between WKY, SHR, and SHRSP clarified the upregulated or downregulated genes depending on cardiac hypertrophy. Furthermore, the gene which shows cardiac hypertrophy dependency at protein expression level was selected. The selected protein was known to be involved in cardiac hypertrophy. However, the known mechanism for the protein was not able to explain the relationship with cardiac hypertrophy. New interaction protein was identified by immunoprecipitation using the antibody against the selected protein and clarified the possibility of involvement in energy production.

Academic Significance and Societal Importance of the Research Achievements

心肥大は高血圧性疾患の大部分を占めており、心不全、脳血管障害、腎障害などを引き起こす原因にもなり得る。更にこれらの疾患は運動機能の低下を引き起こすことで筋力の低下のみならず、身体の恒常性の維持にまで問題が生じ、生活の質や健康寿命に大きな影響を与えることとなる。したがって、効果的な治療を行うことが必要となってくる。しかしながら、治療において降圧薬を使用しても改善がみられず、心肥大が増悪する例も多く存在する。この問題に対し、心筋において心肥大に関与するタンパク質を明らかにし、直接的な標的とすることで心肥大の抑制による高血圧の増悪抑制を目指すことは、治療の可能性が広げることになる。

Research Products

• [Journal Article] Immunohistochemical characterization of granulomatosis with polyangiitis exhibiting spontaneous regression. (2021)
  • Author(s): Yasuhiro Masuta, Yoriaki Komeda, Ikue Sekai, Akane Hara, Masayuki Kurimoto, Keisuke Yoshikawa, Yasuo Otsuka, Ryutaro Takada, Tomoe Yoshikawa, Ken Kamata, Kosuke Minaga, Osamu Maenishi, Tomohiro Watanabe, Masatoshi Kudo
  • Journal Title: Asian Pacific journal of allergy and immunology Volume: -
  • DOI: 10.12932/ap-190221-1073
  • Peer Reviewed / Open Access
• [Journal Article] Intravascular Lymphoma Presenting as a Cavernous Sinus Tumor (2019)
  • Author(s): Kawai S, Okuda T, Fukui A, Sanada Y, Yoshikawa K, Morikawa M, Kuwahara M, Maenishi O, Morita Y, Izumoto S, Kato A, Matsumura I, Kusunoki S
  • Journal Title: Internal Medicine Volume: 58 Issue: 14 Pages: 2085-2089
  • DOI: 10.2169/internalmedicine.1828-18
  • NAID: 130007679533
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2019-07-15
  • Peer Reviewed / Open Access
• [Journal Article] U3-1402 sensitizes HER3-expressing tumors to PD-1 blockade by immune activation (2019)
  • Author(s): Haratani Koji、Yonesaka Kimio、Takamura Shiki、Maenishi Osamu、Kato Ryoji、Takegawa Naoki、Kawakami Hisato、Tanaka Kaoru、Hayashi Hidetoshi、Takeda Masayuki、Maeda Naoyuki、Kagari Takashi、Hirotani Kenji、Tsurutani Junji、Nishio Kazuto、Doi Katsumi、Miyazawa Masaaki、Nakagawa Kazuhiko
  • Journal Title: Journal of Clinical Investigation Volume: 130 Issue: 1 Pages: 374-388
  • DOI: 10.1172/jci126598
  • Peer Reviewed / Open Access
• [Journal Article] Ectopic TWEAKR expression in type I fiber of stroke-prone spontaneously hypertensive rats is related to slow muscle-specific hypotrophy. (2019)
  • Author(s): Inoue T, Hagiyama M, Maenishi O, Kimura M, Mizuguchi N, Mine Y, Kimura R, Chikugo T, Itoh T, Satou T, Ito A
  • Journal Title: Life Sciences Volume: 237 Pages: 116919-116919
  • DOI: 10.1016/j.lfs.2019.116919
  • Peer Reviewed
• [Journal Article] A fungal ball within a maxillary sinus with dental root canal filler and rare fungal propagules (2019)
  • Author(s): Kimura Masatomo、Enomoto Akifumi、Maenishi Osamu、Chikugo Takaaki、Sugita Takashi
  • Journal Title: Pathology International Volume: 69 Issue: 6 Pages: 360-365
  • DOI: 10.1111/pin.12790
  • Peer Reviewed
• [Journal Article] [fam‐] trastuzumab deruxtecan, antitumor activity is dependent on HER2 expression level rather than on HER2 amplification (2019)
  • Author(s): Takegawa Naoki、Tsurutani Junji、Kawakami Hisato、Yonesaka Kimio、Kato Ryoji、Haratani Koji、Hayashi Hidetoshi、Takeda Masayuki、Nonagase Yoshikane、Maenishi Osamu、Nakagawa Kazuhiko
  • Journal Title: International Journal of Cancer Volume: 145 Issue: 12 Pages: 3414-3424
  • DOI: 10.1002/ijc.32408
  • Peer Reviewed
• [Journal Article] Spontaneously infarcted parotid tumours: MRI findings (2019)
  • Author(s): Kashiwagi Nobuo、Hyodo Tomoko、Ishi Kazunari、Maenishi Osamu、Enoki Eisuke、Chikugo Takaaki、Masakatsu Tsurusaki、Yagyu Yukinobu、kitano Mutsukazu、Tomiyama Noriyuki
  • Journal Title: Dentomaxillofacial Radiology Volume: 48 Issue: 5 Pages: 20180382-20180382
  • DOI: 10.1259/dmfr.20180382
  • Peer Reviewed
• [Presentation] ECTOPIC TWEAKR EXPRESSION IN TYPE I FIBER OF STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS IS RELATED TO SLOW MUSCLE-SPECIFIC HYPOTROPHY THROUGH MURF1 OVEREXPRESSION (2021)
  • Author(s): Takao Inoue, Man Hagiyama, Osamu Maenishi, Masatomo Kimura, Nobuyuki Mizuguchi, Yoshihiro Mine, Ryuichiro Kimura, Takaaki Chikugo, Tatsuki Itoh, Takao Satou, Akihiko Ito
  • Organizer: International Society for Hypertension 2021
  • Int'l Joint Research
• [Presentation] SHRSPでは廃用性筋萎縮からの回復が遅延する (2021)
  • Author(s): 井上敬夫、金澤佑治、水口信行、峯 嘉宏、前西 修、木村雅友、萩山 満、米重あづさ、和田昭裕、筑後孝章、伊藤龍生、佐藤隆夫、伊藤彰彦
  • Organizer: 第57回 高血圧関連疾患モデル学会
• [Presentation] 脳卒中発症ラットSHRSPは廃用性萎縮からの回復時に筋線維の損傷がみられない (2021)
  • Author(s): 井上敬夫、金澤佑治、水口信行、峯 嘉宏、前西 修、木村雅友、萩山 満、米重あづさ、和田昭裕、筑後孝章、伊藤龍生、佐藤隆夫、伊藤彰彦
  • Organizer: 第7回 日本筋学会学術集会
• [Presentation] 発育低下のみられる骨格筋におけるTNF関連受容体の発現異常 (2020)
  • Author(s): 井上 敬夫、萩山 満、前西 修、木村 雅友、水口 信行、峯 嘉宏、筑後 孝章、伊藤 龍生、佐藤 隆夫、伊藤 彰彦
  • Organizer: 日本農芸化学会 2020年度大会
• [Presentation] 遅筋特異的発育異常におけるMuRF1の発現上昇と上流因子の解析 (2019)
  • Author(s): 井上敬夫、前西修、木村雅友、萩山満、水口信行、峯嘉宏、筑後孝章、伊藤龍生、佐藤隆夫、伊藤彰彦
  • Organizer: 第5回 日本筋学会