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

2013 Fiscal Year Final Research Report

• 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
• Keywords: アポトーシス / シグナル

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] 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
• [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
  • Year and Date: 20121103-07
• [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
  • Year and Date: 20121103-07
• [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
  • Year and Date: 20121026-27