Immune surveillance is involved in cardiomyocyte death in diseased hearts

• Project/Area Number: 25670193
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Osaka University
• Principal Investigator: FUJIO Yasushi 大阪大学, 薬学研究科(研究院), 教授 (20359839)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 心筋細胞 / 心不全 / 免疫学的監視機構 / 心筋細胞死 / 細胞傷害

Outline of Final Research Achievements

Since cardiac myocytes cease to proliferate immediately after birth in mammalian hearts, cardiomyocyte death, induced by cardiovascular diseases, results in the reduction of cardiomyocytes in number, leading to cardiac dysfunction. In this context, the prevention of cardiomyocyte death is a promising therapeutic strategy against heart failure.
In this study, we have revealed that immune surveillance system is involved in cardiac cell daeth in the process of cardiac remodling after myocardial infarction. It could be proposed that immunosurvaillance system is a novel therapeutic target against heart failure.

Research Products

• [Journal Article] The Inhibition of N-Glycosylation of Glycoprotein 130 Molecule Abolishes STAT3 Activation by IL-6 Family Cytokines in Cultured Cardiac Myocytes. (2014)
  • Author(s): Matsuo R, Morihara H, Mohri T, Murasawa S, Takewaki K, Nakayama H, Maeda M, Fujio Y.
  • Journal Title: PLoS One Volume: 23 Issue: 10 Pages: e111097-e111097
  • DOI: 10.1371/journal.pone.0111097
  • Peer Reviewed / Open Access
• [Journal Article] Requirement of SLD5 for Early Embryogenesis. (2013)
  • Author(s): Mohri T
  • Journal Title: PLoS One Volume: 8 Issue: 11 Pages: e78961-e78961
  • DOI: 10.1371/journal.pone.0078961
  • Peer Reviewed
• [Journal Article] Cathelicidin antimicrobial peptide inhibits fibroblast migration via P2X7 receptor signaling. (2013)
  • Author(s): Kumagai, S., Matsui, K., Kawaguchi, H., Yamashita, T., Mohri, T., Fujio, Y., Nakayama, H.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 437 Issue: 4 Pages: 609-614
  • DOI: 10.1016/j.bbrc.2013.07.010
  • Peer Reviewed
• [Journal Article] Polymorphisms of CYP2D6 gene and gefitinib-induced hepatotoxicty. (2013)
  • Author(s): Takimoto, T., Kijima, T., Otani, Y., Nonen, S., Namba, Y., Mori, M., Yokota, S., Minami, S., Komuta, K., Uchida, J., Imamura, F., Furukawa, M., Tsuruta, N., Fujio, Y., Azuma, J., Tachibana, I., Kumanogoh, A.
  • Journal Title: Clin. Lung Cancer. Volume: 14 Issue: 5 Pages: 502-507
  • DOI: 10.1016/j.cllc.2013.03.003
  • Peer Reviewed
• [Journal Article] Minimal dose for effective clinical outcome and predictive factors for responsiveness to carvedilol: Japanese chronic heart failure (J-CHF) study. (2013)
  • Author(s): Okamoto, H., Hori, M., Matsuzaki, M., Tsutsui, H., Yamazaki, T., Nagai, R., Yoshikawa, T., Fujio, Y., Nonen, S. Azuma, J., Izumi, T., Ohashi, Y., Kitabatake, A. on behalf of J-CHF investigators.
  • Journal Title: Int. J. Cardiol. Volume: 164 Issue: 2 Pages: 238-244
  • DOI: 10.1016/j.ijcard.2012.11.051
  • Peer Reviewed
• [Journal Article] NAT2 genotype guided regimen reduces isoniazid-induced liver injury and early treatment failure in the 6-month four-drug standard treatment of tuberculosis: A randomized controlled trial for pharmacogenetics-based therapy. (2013)
  • Author(s): Azuma, J. Ohno, M., Kubota, R., Yokota, S., Nagai, T., Tsuyuguchi, K., Okuda, Y., Takashima, T., Kamimura, S., Fujio, Y., Kawase, I. and Pharmacogenetics-based tuberculosis research group.
  • Journal Title: Eur. J. Clin. Pharmacol. Volume: 69 Issue: 5 Pages: 1091-1101
  • DOI: 10.1007/s00228-012-1429-9
  • Peer Reviewed
• [Journal Article] Genetic polymorphisms of CYP17A1 in steroidogenesis pathway are associated with risk of progression to castration-resistant prostate cancer in Japanese men receiving androgen deprivation therapy (2012)
  • Author(s): Takeshi Yamada, Masashi Nakayama, Tomohito Shimizu, Shinpei Nonen, et al.
  • Journal Title: Int J Clin Oncol Volume: (in press) Issue: 4 Pages: 711-718
  • DOI: 10.1007/s10147-012-0430-8
  • Peer Reviewed
• [Presentation] Interleukin 27 induces endothelial differentiation in murine cardiac stem cells. (2015)
  • Author(s): 田中智大、尾花理徳、前田真貴子、中山博之、藤尾慈
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] Elucidation of molecular mechanism of cardiomyocyte necrosis induced by reactive oxygen species. (2015)
  • Author(s): 土山大介、中山博之、森原啓文、石田瑛子、尾花理徳、前田真貴子、藤尾慈
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] IL-27 negatively regulates murine experimental autoimmune myocarditis (EAM). (2015)
  • Author(s): 古谷知佳、宮脇昭光、大谷勇太、尾花理徳、前田真貴子、中山博之、藤尾慈
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] Adrenergic receptors β2 and β3 transduce differential signalsin cardiac fibroblasts. (2015)
  • Author(s): 五十嵐裕美、中山博之、松浪佐知、早水菜穂、舎川洸太、尾花理徳、前田真貴子、藤尾慈
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] The properties of cardiac Sca-1+ resident stem cells are altered in response to myocardial inflammation. (2015)
  • Author(s): 松原由実、宮脇昭光、榎原正貴、尾花理徳、前田真貴子、中山博之、藤尾慈
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] Caveolae-specific phosphorylation of L-type calcium channel b2a subunit exaggerates cardiac hypertrophic responses after a1 adrenergic stimulation in mice. (2014)
  • Author(s): Nakayama, H., Kumagai, S., Matsunami, S., Hayamizu, N, Tonegawa, K., Otsuka, W., Fujio, Y.
  • Organizer: International Society of Heart Research 日本部会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-11-28 – 2014-11-29
• [Presentation] Administration of phospholamban-antisense locked nucleic acid improves cardiac contractility in a murine heart failure model (2014)
  • Author(s): 森原 啓文, 中山 博之, 大岩 晴矩, 土山 大介, 山本 剛史, 小比賀 聡, 藤尾 慈
  • Organizer: 第18回 日本心不全学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-10 – 2014-10-12
• [Presentation] The overexpression of CD93 in myeloid cells attenuated the cardiac fibrosis after myocardial infarction (2014)
  • Author(s): 大谷 勇太、竹脇 佳那、宮本 香織、尾花 理徳、中山 博之、藤尾 慈
  • Organizer: 第18回 日本心不全学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-10 – 2014-10-12
• [Presentation] 心疾患におけるgp130サイトカインの役割：新たな治療法の開発を目指して (2014)
  • Author(s): 藤尾 慈、葭山 稔
  • Organizer: 日本薬学会134会年会
  • Place of Presentation: 熊本
  • Invited
• [Presentation] BIN1の過剰発現は心筋細胞死を介して心筋リモデリングを増悪する (2014)
  • Author(s): 舎川洸太，松浪佐知，土山大介，中山博之，藤尾慈
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台
• [Presentation] マクロファージ特異的なCD93過剰発現による死細胞貪食の増強は心筋梗塞後の心筋線維化を抑制する (2014)
  • Author(s): 竹脇佳那，山下朋美，宮本香織，毛利友美，中山博之，藤尾慈
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台
• [Presentation] L型カルシウムチャネルβ2aサブユニットのリン酸化は心筋細胞肥大を惹起する (2014)
  • Author(s): 早水菜穂，熊谷渉平，松浪佐知，中山博之，藤尾慈
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台
• [Presentation] 心血管病におけるサイトカイン医科学-gp130サイトカインと心筋保護 (2013)
  • Author(s): 藤尾 慈
  • Organizer: 生体機能と創薬シンポジウム2013
  • Place of Presentation: 福岡
  • Invited
• [Presentation] Inhibition of P2X7 Receptor Signaling Promotes Adverse Cardiac Remodeling after Myocardial Infarction through Enhanced Cardiac Fibroblast Migration (2013)
  • Author(s): Shohei Kumagai, Hiroyuki Nakayama, Akimitsu Miyawaki, Tomomi Mohri, Yasushi Fujio
  • Organizer: The American Heart Association Scientific Sessions 2013
  • Place of Presentation: Dallas, Texas, USA
• [Presentation] A report From the Japanese pharmacogenomics clinical trial; CYP2A6 Gene Polymorphisms Influence Nicotine Dependence and Monoamine Oxidase Gene Polymorphism Does Smoking Cessation Behavior (2013)
  • Author(s): Makiko Maeda, Yaushi Fujio, Yasuhiko Takemoto, Junichi Azuma
  • Organizer: The American Heart Association Scientific Sessions 2013
  • Place of Presentation: Dallas, Texas, USA