Analysis of dilated cardiomyopathy phenotyoe in cardiac-specific SOCS3 deficient mice.

• Project/Area Number: 26461137
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kurume University
• Principal Investigator: Yasukawa Hideo 久留米大学, 医学部, 准教授 (60289361)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 心不全 / 拡張型心筋症 / 心筋細胞 / SOCS3 / JAK-STAT / オートファジー / Jak-STAT / 血管平滑筋細胞 / 線維化 / STAT3 / 加齢 / 平滑筋

Outline of Final Research Achievements

Suppressor of cytokine signaling-3 (SOCS3) is a cytokine-inducible negative regulator of JAK-STAT signaling pathway. Cardiac-specific SOCS3 deficient mice (SOCS3-CKO) spontaneously develop cardiac dysfunction with advanced age. In this study, we analysed the underlying mechanism of age-related cardiac dysfunction in SOCS3-cKO mice. We found that developed cardiac dysfunction estimated by echocardiogram and increased activation of STAT3 from 25 weeks of age in SOCS3-CKO. In SOCS3-CKO mice hearts from 25 weeks of age, LC3II/LC3I ratio was significantly decreased. Western blot analysis revealed that expression of parkin and PINK1 but not p62 and Bnip3 were decreased in SOCS3-CKO mice compared with control mice from 25 weeks of age. These results suggest that age-related cardiac dysfunction in SOCS3-CKO mice may be due to impaired autophagy through sustained STAT3 activation.

Research Products

• [Journal Article] Disturbance of cardiac gene expression and cardiomyocyte structure predisposes Mecp2-null mice to arrhythmias. (2015)
  • Author(s): Hara M, Takahashi T, Mistumasu C, Igata S, Takano M, Minami T, Yasukawa H, Okayama S, Nakamura K, Okabe Y, Tanaka E, Takemura G, Kosai K, Yamashita Y, Matsuishi T.
  • Journal Title: Sci Rep Volume: 5 Issue: 1 Pages: 11204-11204
  • DOI: 10.1038/srep11204
  • Peer Reviewed / Open Access
• [Journal Article] Cardiac-Specific SOCS3 Deletion Prevents in vivo myocardial ischemia reperfusion injury through sustained activation of cardioprotective signaling Molecules. (2015)
  • Author(s): Nagata T, Yasukawa H, Kyogoku S, Oba T, Takahashi J, Nohara S, Minami T, Mawatari K, Sugi Y, Shimozono K, Pradervand S, Hoshijima M, Aoki H, Fukumoto Y, Imaizumi T.
  • Journal Title: PLOS ONE Volume: 10 Issue: 5 Pages: e0127942-e0127942
  • DOI: 10.1371/journal.pone.0127942
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Renal Nerve-Mediated Erythropoietin Release Confers Cardioprotection During Remote Ischemic Preconditioning (2015)
  • Author(s): Oba T, Yasukawa H, Nagata T, Kyogoku S, Minami T, Nishihara M, Ohshima H, Mawatari K, Nohara S, Takahashi J, Sugi S, Igata S, Iwamoto Y, Kai H, Matsuoka H, Takano M, Aoki H, Fukumoto Y, Imaizumi I.
  • Journal Title: Circulation Journal Volume: 79 Issue: 7 Pages: 1557-1567
  • DOI: 10.1253/circj.CJ-14-1171
  • NAID: 130005083944
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] ETS transcription factor ETV2 directly converts human fibroblasts into functional endothelial cells. (2015)
  • Author(s): Morita R, Suzuki M, Kasahara H, Shimizu N, Shichita T, Sekiya T, Kimura A, Sasaki K, Yasukawa H, Yoshimura A.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 112 Issue: 1 Pages: 160-165
  • DOI: 10.1073/pnas.1413234112
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Cardiac-Specific SOCS3 deletion prevents in vivo myocardial ischemia reperfusion injury through sustained activation of cardioprotective signaling molecules. (2015)
  • Author(s): Nagata T, Yasukawa H, Kyogoku S, Oba T, Takahashi J, Nohara S, Minami T, Mawatari K, Sugi Y, Shimozono K, Pradervand S, Hoshijima M, Aoki H, Fukumoto Y, Imaizumi T.
  • Journal Title: PLOS ONE Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Omentin prevents myocardial ischemic injury through AMP-activated protein kinase- and Akt-dependent mechanisms. (2014)
  • Author(s): Kataoka Y, Shibata R, Ohashi K, Kambara T, Enomoto T, Uemura Y, Ogura Y, Yuasa D, Matsuo K, Nagata T, Oba T, Yasukawa H, Numaguchi Y, Sone T, Murohara T, Ouchi N.
  • Journal Title: J Am Coll Cardiol Volume: 63 Issue: 24 Pages: 2722-2733
  • DOI: 10.1016/j.jacc.2014.03.032
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Protective role of JAK/STAT signaling against renal fibrosis in mice with unilateral ureteral obstruction. (2013)
  • Author(s): Koike K, Ueda S, Yamagishi S, Yasukawa H, Kaida Y, Yokoro M, Fukami K, Yoshimura A, Okuda S.
  • Journal Title: Clin Immunol Volume: 150 Issue: 1 Pages: 78-87
  • DOI: 10.1016/j.clim.2013.11.003
  • Peer Reviewed
• [Journal Article] Alterations in coxsackievirus and adenovirus receptor confer susceptibility to ventricular arrhythmia with an ischemic event. (2013)
  • Author(s): Yasukawa H, Oba T, Fukumoto Y.
  • Journal Title: J Am Coll Cardiol Volume: 63 Issue: 6 Pages: 560-562
  • DOI: 10.1016/j.jacc.2013.12.001
  • Peer Reviewed / Open Access
• [Presentation] Synergistic Reduction of Myocardial Ischemia Reperfusion Injury by Ischemic Preconditioning and Myocardial SOCS3 Deficiency in Mice. (2016)
  • Author(s): Nohara S, Nagata T, Yasukawa H, Sugi Y, Mawatari K, Fukui D, Kyogoku S, Ohshima H, Minami T, Takahashi J, Shimozono K, Shibata T, Fukumoto Y
  • Organizer: The American Heart Association, The 89th Scientific Session
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2016-11-12
• [Presentation] 心不全と睡眠時無呼吸症候群を合併したムコリピドーシスⅢ型の一例 (2016)
  • Author(s): 下園 弘達、 安川 秀雄、 永田 隆信、 野原 正一郎、 髙橋 甚彌、 佐々木 知子、 柴田 龍宏、 福井 大介、 馬渡 一寿、 杉 雄介、 福本 義弘
  • Organizer: 第64回日本心臓病学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2016-09-23
• [Presentation] 当院循環器内科で経験したFabry病の12症例についてのまとめ (2016)
  • Author(s): 馬渡一寿、安川秀雄、永田隆信、下園弘達、野原正一郎、髙橋甚彌、佐々木知子、柴田龍宏、福井大介、杉雄介、福本義弘
  • Organizer: 第64回日本心臓病学会学術集会
  • Place of Presentation: 東京
• [Presentation] Cardiac-Specific SOCS3 deficiency leads to left ventricular dysfunction with advanced age through impaired autophagy (2015)
  • Author(s): Nohara S, Yasukawa H, Oba T, Nagata T, Takahashi J, Shimozono K, Minami T, Fukui D, Mawatari K, Sugi Y, Fukumoto Y.
  • Organizer: The American Heart Association, The 89th Scientific Sessions
  • Place of Presentation: 米国オーランド
  • Year and Date: 2015-11-07
  • Int'l Joint Research
• [Presentation] 心筋特異的 SOCS3 欠損による心筋虚血再灌流障害における転写プロファイリング応答の変化 (2015)
  • Author(s): 永田隆信、安川秀雄、高橋甚彌、下園弘達、野原正一郎、南知子、大場豊治、馬渡一寿、杉雄介、福本義弘
  • Organizer: 第19回日本心不全学会学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2015-10-22
• [Presentation] 心筋特異的SOCS3ノックアウトマウスは加齢に伴いオートファジー障害によって左心収縮不全を呈する (2015)
  • Author(s): 野原正一郎、安川秀雄、大場豊治、永田隆信、高橋甚彌、下園弘達、南知子、馬渡一寿、杉雄介、福本義弘
  • Organizer: 第19回日本心不全学会学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2015-10-22
• [Presentation] 心筋特異的SOCS3欠損マウスにおけるドキソルビシン誘発性心筋障害の抑制機構 (2015)
  • Author(s): 京極幸子、安川秀雄、永田隆信、野原正一郎、高橋甚彌、下園弘達、南知子、馬渡一寿、杉雄介、今泉勉、福本義弘
  • Organizer: 第63回日本心臓病学会学術集会
  • Place of Presentation: 横浜市
  • Year and Date: 2015-09-18
• [Presentation] 心筋特異的SOCS3欠損は持続的な心筋保護シグナルの活性化を介して心筋虚血再灌流障害を抑制する (2015)
  • Author(s): 永田隆信、安川秀雄、京極幸子、下園弘達、野原正一郎、高橋甚彌、大島英樹、大場豊治、福井大介、馬渡一寿、杉雄介、今泉勉、福本義弘
  • Organizer: 第63回日本心臓病学会学術集会
  • Place of Presentation: 横浜市
  • Year and Date: 2015-09-18
• [Presentation] 心筋特異的SOCS3ノックアウトマウスは加齢に伴いオートファジー障害によって左心収縮不全を呈する (2015)
  • Author(s): 安川秀雄、大場豊治、永田隆信、南知子、高橋甚彌、野原正一郎、福本義弘
  • Organizer: 第15回日本抗加齢医学会総会
  • Place of Presentation: 福岡市
  • Year and Date: 2015-05-29
• [Presentation] ERK1/2 suppressor sprouty4 does not play an important role in the development of left ventricular remodeling after acute myocardial infarction. (2014)
  • Author(s): Mawatari K、Yasukawa H、Oba T、Futamata N、Nagata N、Kyougoku S、Ohshima H、Imaizumi T
  • Organizer: 第31回国際心臓研究学会（ISHR）
  • Place of Presentation: ウインク愛知（愛知県名古屋市）
  • Year and Date: 2014-11-29
• [Presentation] Cardiac-Specific SOCS3 Knockout Mice by enhanced activation of cardioprotective signaling pathways. (2014)
  • Author(s): Nagata T, Yasukawa H, Oba T, Pradervand S, Mawatari K, Kyogoku S, Ohshima H, Minami T, Sasaki K, Yajima T, Hoshijima H, Knowlton KU,Imaizumi T, Fukumoto Y
  • Organizer: 第18回日本心不全学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2014-10-11
• [Presentation] エリスロポイエチンはremote ischemic preconditioningにおける心筋保護機構に重要である (2014)
  • Author(s): 安川秀雄、大場豊治、永田隆信、今泉勉、福本義弘
  • Organizer: 第62回日本心臓病学会学術集会
  • Place of Presentation: 仙台市民会館（宮城県仙台市）
  • Year and Date: 2014-09-27
• [Presentation] 心肥大症例におけるαガラクトシダーゼのE66Q遺伝子変異について (2014)
  • Author(s): 安川秀雄、馬渡一寿、今泉勉
  • Organizer: 第62回日本心臓病学会学術集会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2014-09-27
• [Presentation] Mechanism of cardioprotection against myocardial infarction by renal nerve-mediated Inter- organ communication. (2014)
  • Author(s): Yasukawa H, Oba T, Nagata T, Fukumoto Y.
  • Organizer: The 18th International Vascular Biology Meeting
  • Place of Presentation: みやこめっせ（京都府京都市）
  • Year and Date: 2014-04-14
• [Remarks] 久留米大学医学部心臓血管内科
• [Remarks] 久留米大学循環器病研究所
• [Remarks] 久留米大学医学部心臓・血管内科
  • URL: http://www.kurume-shinzo.com
• [Remarks] 久留米大学 循環器病研究所
  • URL: http://kurume-junken.com
• [Remarks] 久留米大学心臓血管内科
• [Remarks] kurume-shinzo.com