efficacy and role of signaling pathway by SOCS3-CKO in myocardial ischemia repercussion injury

• Project/Area Number: 24791957
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Emergency medicine
• Research Institution: Kurume University
• Principal Investigator: NAGATA Takanobu 久留米大学, 医学部, 助教 (50535078)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: アポトーシス / シグナル / 救急医学 / 集中治療医学

Research Abstract

We investigated the role of myocardial suppressor of cytokine signaling-3 (SOCS3), an intrinsic negative feedback regulator of the JAK-STAT signaling pathway, in the pathophysiology of myocardial ischemia-reperfusion(I/R) injury. Activation of cardioprotective signaling pathways including STAT3, AKT, and ERK1/2 were rapidly peaked and was inactivated after I/R. Although the initial infarct size after coronary occlusion determined by triphenyltetrazolium chloride staining was comparable between control and cardiac-specific SOCS3 knockout mice (SOCS3-CKO), the infarct size 24 h after I/R was reduced by approximately 30% in SOCS3-CKO mice, indicating that progression of myocardial I/R injury was prevented in SOCS3-CKO hearts. Cardiac-specific SOCS3 deletion enhanced multiple cardioprotective signaling pathways including STAT3, AKT and ERK1/2 while inhibiting myocardial apoptosis.

Research Products

• [Journal Article] Screening for Fabry disease in patients with left ventricular hypertrophy. (2013)
  • Author(s): Mawatari K, Nagata T
  • Journal Title: Int J Cardiol Volume: 3 Pages: 1059-1061
  • Peer Reviewed
• [Journal Article] Screening for Fabry disease in patients with left ventricular hypertrophy. (2013)
  • Author(s): Mawatari K, Yasukawa H, Oba T, Nagata T, Togawa T, Tsukimura T, Kyogoku S, Ohshima H, Minami T, Sugi Y, Sakuraba H, Imaizumi T.
  • Journal Title: Int J Cardiol Volume: 167 Issue: 3 Pages: 1059-1061
  • DOI: 10.1016/j.ijcard.2012.10.076
  • Peer Reviewed
• [Journal Article] Cardiomyocyte-specific transgenic expression of lysyl oxidase-like protein-1 induces cardiac hypertrophy in mice (2012)
  • Author(s): Ohmura H, Yasukawa H, Minami T, Sugi Y, Oba T, Nagata T, Kyogoku S, Ohshima H, Aoki H, Imaizumi T
  • Journal Title: Hypertens Res Volume: 35(11) Pages: 1063-1068
  • Peer Reviewed
• [Journal Article] Transient reduction and activation of circulating dendritic cells in patients with acute myocardial infarction (2012)
  • Author(s): Fukui D, Yasukawa H, Sugi Y, Oba T, Nagata T, Kyogoku S, Futamata N, Yokoyama T, Yokoyama S, Kai H, Ueno T, Kage M, Imaizumi T
  • Journal Title: Int J Cardiol Volume: 160(3) Pages: 216-219
  • Peer Reviewed
• [Journal Article] Cardiac-specific deletion of SOCS-3 prevents development of left ventricular remodeling after acute myocardial infarction (2012)
  • Author(s): Oba T, Yasukawa H, Hoshijima M, Sasaki K, Futamata N, Fukui D, Mawatari K, Nagata T, Kyogoku S, Ohshima H, Minami T, Nakamura K, Kang D, Yajima T, Knowlton KU, Imaizumi T
  • Journal Title: J Am Coll Cardiol Volume: 59(9) Pages: 838-852
  • Peer Reviewed
• [Journal Article] Cardiac-Specific Deletion of SOCS-3 Prevents Development of Left Ventricular Remodeling After Acute Myocardial Infarction. (2012)
  • Author(s): Oba T, Yasukawa H, Hoshijima M, Sasaki KI, Futamata N, Fukui D, Mawatari K, Nagata T, Kyogoku S, Ohshima H, Minami T, Nakamura K, Kang D, Yajima T, Knowlton KU, Imaizumi T
  • Journal Title: J Am Coll Cardiol Volume: 59 Pages: 838-852
  • Peer Reviewed
• [Journal Article] Cardiomyocyte-specific transgenic expression of lysyl oxidase-like protein-1 induces cardiac hypertrophy in mice. (2012)
  • Author(s): Ohmura H, Yasukawa H, Minami T, Sugi Y, Oba T, Nagata T, Kyogoku S, Ohshima H, Aoki H, Imaizumi T
  • Journal Title: Hypertens Res Volume: 35 Pages: 1063-1068
  • Peer Reviewed
• [Journal Article] Transient reduction and activation of circulating dendritic cells in patients with acute myocardial infarction. (2012)
  • Author(s): Fukui D, Yasukawa H, Sugi Y, Nagata T, Kyogoku S, Futamata N, Oba T, Yokoyama T, Yokoyama S, Ueno T, Kage M, Imaizumi T
  • Journal Title: Int J Cardiol Volume: 160 Pages: 216-219
  • Peer Reviewed
• [Journal Article] SOCS3: a novel therapeutic target for cardioprotection. (2012)
  • Author(s): Yasukawa H, Nagata T, Oba T, Imaizumi T
  • Journal Title: Jak-Stat Volume: 1 Pages: 234-240
  • Peer Reviewed
• [Presentation] Screening for fabry disease in patients with left ventricular hypertrophy. (2013)
  • Author(s): 馬渡一寿、永田隆信
  • Organizer: 第17回に本心不全学会学術集会
  • Place of Presentation: 埼玉
• [Presentation] Cardiac-specific deletion of suppressor of cytokine signaling-3 prevents doxorubisin-induced cardiomyopathy in mice (2012)
  • Author(s): Kyogoku S, Yasukawa H, Nagata T, Oba T, Ohshima H, Minami T, Yajima T, Hoshijima M, Aoki H, Knowlton KU, Imaizumi T
  • Organizer: The American Heart Association, The 85th Scientific Sessions
  • Place of Presentation: Los Angeles, USA
• [Presentation] Pioglitazone decreases plasma fibroblast growth factor-21 levels in patients with type 2 diabetes (2012)
  • Author(s): Mawatari K, Tahara N, Yasukawa H, Oba T, Nagata T, Kyogoku S, Ohshima H, Minami T, Mizoguchi M, Sugi Y, Adachi H, Imaizumi T
  • Organizer: The American Heart Association, The 85th Scientific Sessions
  • Place of Presentation: Los Angeles, USA
• [Presentation] Prevention of doxorubicin-induced cardiomyopathy in cardiac-specific SOCS3 deficient mice by preserving energy metabolism (2012)
  • Author(s): Kyogoku S, Yasukawa H, Nagata T, Oba T, Ohshima H, Minami T, Fukui D, Sugi Y, Aoki H, Imaizumi T
  • Organizer: 第29回国際心臓研究学会(ISHR)日本部会総会
  • Place of Presentation: 福岡
• [Presentation] Cardiac-Specific Deletion of Suppressor of Cytokine Signaling-3 Prevents Doxorubicin-Induced Cardiomyopathy in Mice. (2012)
  • Author(s): Kyogoku S, Yasukawa H, Nagata T, Oba T, Ohshima H, Minami T, Yajima T, Hoshijima M, Aoki H, Knowlton KU, Imaizumi T
  • Organizer: The American Heart Association, The 85th Scientific Sessions
  • Place of Presentation: Los Angels, USA
• [Presentation] Pioglitazone Decrease Plasma Fibroblast Growth Factor-21 Levels in Patients with Type 2 (2012)
  • Author(s): Mawatari K, Tahara N, Yasukawa H, Oba T, Nagata T, Kyogoku S, Ohshima H, Minami T, Mizoguchi M, Sugi Y, Adachi H, Imaizumi T
  • Organizer: The American Heart Association, The 85th Scientific Sessions
  • Place of Presentation: Los Angels, USA
• [Presentation] Prevention of Doxorubicin-induced Cardiomyopathy in Cardiac-Specific SOCS3 Deficient Mice by Preserving Energy Metabolism. (2012)
  • Author(s): Kyogoku S, Yasukawa H, Nagata T, Oba T, Ohshima H, Minami T, Fukui D, Sugi Y, Aoki H, Imaizumi T
  • Organizer: 第29回 国際心臓研究学会 ISHR 日本部会総会
  • Place of Presentation: 福岡
• [Presentation] Prevention of Doxorubicin-Induced Cardiomyopathy in Cardiac-Specific SOCS3 Deficient Mice by Augmenting STAT3 Signaling Pathway (2012)
  • Author(s): 京極 幸子、安川秀雄、永田隆信、大場豊治、大島英樹、南知子、福井大介、杉雄介、青木浩樹、今泉勉
  • Organizer: 第36回 心筋代謝研究会
  • Place of Presentation: 東京