Analyses of biological significance of STAT3/Pim-1 signaling in cardiac stem cells

• Project/Area Number: 25860061
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pharmacology in pharmacy
• Research Institution: Osaka University
• Principal Investigator: Mohri Tomomi 大阪大学, 薬学研究科(研究院), 研究員 (20572960)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: サイトカイン / 心筋組織幹細胞 / IL-27 / Pim-1 / 血管内皮細胞 / STAT3 / 組織幹細胞 / IL-6ファミリーサイトカイン / 心臓 / 血管新生

Outline of Final Research Achievements

Since cardiomyocytes cease to proliferate immediately after birth, it has been believed that hearts have limited capacity of regeneration. Recently, several kinds of cardiac resident stem cells have been identified and much attention has been paid to their biological functions. So far, we revealed that that IL-6 family cytokines induce endothelial differentiation of cardiac Sca-1+ stem cells through STAT3/Pim-1 pathway. In this study, we have demonstrated that the myocardial expression of IL-27, a member of IL-6 cytokine family, is upregulated at chronic phase of myocardial infarction and myocarditis and that IL-27 functions as a novel regulator of the trans-differentiation of cardiac stem cells into endothelial cells through STAT3/Pim-1 pathway. We also explored the downstream targets of STAT3/Pim-1 pathway and identified a candidate substrate of Pim-1 kinase in cardiac stem cells.

Research Products

• [Journal Article] Interleukin-27 induces the endothelial differentiation in Sca-1+ cardiac resident stem cells. (2015)
  • Author(s): Tanaka, T., Obana, M., Mohri, T., Maeda, M., Fujio, Y.
  • Journal Title: Cytokine Volume: 75 Issue: 2 Pages: 365-372
  • DOI: 10.1016/j.cyto.2015.06.009
  • Peer Reviewed / Open Access
• [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
• [Presentation] 心筋梗塞慢性期における心筋特異的 STAT3 の欠損は心筋リモデリング (2014)
  • Author(s): 榎本 大智、尾花 理徳、宮脇 昭光、毛利 友美、前田 真貴子、中山 博之、藤尾 慈
  • Organizer: 生体機能と創薬シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2014-08-28 – 2014-08-29
• [Presentation] The macrophage-specific overexpression of CD93 enhances phagocytosis and ameliorates cardiac fibrosis after myocardial infarction (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: 仙台国際センター（宮城県仙台市）
• [Presentation] Deficiency of P2X7 receptor signaling promotes adverse cardiac remodeling after myocardial infarction through enhanced cardiac fibroblast migration (2013)
  • Author(s): 熊谷渉平、中山博之、宮脇昭光、毛利友美、藤尾慈
  • Organizer: 第21回日本血管生物医学会学術集会
  • Place of Presentation: 千里阪急ホテル（大阪府豊中市）
• [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 Convention Center (Dallas, Texas, USA)
• [Presentation] マクロファージによる死細胞貪食は心筋梗塞後の病態形成を抑制する
  • Author(s): 竹脇佳那、宮本香織、尾花理徳、山下朋美、毛利友美、中山博之、藤尾慈
  • Organizer: 第124回日本薬理学会近畿部会
  • Place of Presentation: 京都ガーデンパレス（京都府京都市）