Application of exosomal molecules as exposure dose assessment markers

• Project/Area Number: 15K15443
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Hirosaki University
• Principal Investigator: KASHIWAKURA IKUO 弘前大学, 保健学研究科, 教授 (00177370)
• Co-Investigator(Kenkyū-buntansha): 三浦 富智 弘前大学, 保健学研究科, 准教授 (20261456) ; 千葉 満 弘前大学, 保健学研究科, 講師 (20583735)
• Co-Investigator(Renkei-kenkyūsha): MONZEN Satoru 弘前大学, 大学院保健学研究科, 講師 (20514136) ; YOSHINO Hironori 弘前大学, 大学院保健学研究科, 助教 (10583734)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 被ばく医療 / マイクロRNA / 染色体異常解析 / 被ばくマーカー / エキソソーム / miRNA

Outline of Final Research Achievements

We performed array analysis of microRNA (miRNA) in serum obtained from 1-5 Gy X-ray whole-body irradiated mice and examined the relationship of miRNA expression after irradiation with dose and time. We identified one type of miRNA whose expression increased in a dose-dependent manner immediately after irradiation and 11 others whose expression decreased 24 h after irradiation. However, in the initial method employed for total RNA recovery, we used blood from several mice; as a result, we were unable to observe differences in miRNA expression among individual mice and obtain reproducible results. Therefore, we found a method that can extract and analyze high-quality RNA from individual mice. We are currently advancing miRNA expression analysis using an improved method. In addition, hierarchical clustering analysis based on array analysis of miRNA has revealed fluctuating expressions of genes associated with platelet function. Further investigation is underway.

Research Products

• [Journal Article] Effects of endoplasmic reticulum stress on apoptosis induction in radioresistant macrophages. (2017)
  • Author(s): Yoshino H, Kumai Y, Kashiwakura.
  • Journal Title: Molecular Medicine Reports Volume: 15(5) Issue: 5 Pages: 2867-2872
  • DOI: 10.3892/mmr.2017.6298
  • Peer Reviewed
• [Journal Article] Exosomes derived from SW480 colorectal cancer cells promote cell migration in HepG2 hepatocellular cancer cells via the mitogen-activated protein kinase pathway. (2016)
  • Author(s): M. Chiba , N. Watanabe , M. Watanabe , M. Sakamoto , A. Sato , M. Fujisaki , S. Kubota , S. Monzen , A. Maruyama , N. Nanashima , I. Kashiwakura , T. Nakamura .
  • Journal Title: International Journal of Oncology Volume: 48(1) Issue: 1 Pages: 305-312
  • DOI: 10.3892/ijo.2015.3255
  • Peer Reviewed / Open Access
• [Journal Article] Expression analysis of radiation-responsive genes in human hematopoietic stem/progenitor cells. (2016)
  • Author(s): T. Tsujiguchi , T. Hirouchi , S. Monzen , Y. Tabuchi , I. Takasaki , T. Kondo , I. Kashiwakura.
  • Journal Title: Journal of Radiation Research Volume: 57(1) Issue: 1 Pages: 35-43
  • DOI: 10.1093/jrr/rrv071
  • Peer Reviewed / Open Access
• [Journal Article] Radiomitigative Effects of Grifola frondosa Preparations on Mice Exposed to Lethal Ionizing Irradiation. (2016)
  • Author(s): K. Yokoyama, M. Yamaguchi, A. Nishiyama, S. Murakami, A. Tanaka, M. Hosoda, I. Kashiwakura.
  • Journal Title: Jacobs Journal of Food and Nutrition Volume: 2(3) Pages: 22-25
  • Peer Reviewed / Open Access
• [Journal Article] Characteristics of human CD34+ cells exposed to ionizing radiation under cytokine-free conditions. (2015)
  • Author(s): J. Ishikawa, N. Hayashi, M. Yamaguchi, S. Monzen, I. Kashiwakura.
  • Journal Title: Journal of Radiation Research Volume: 56(4) Issue: 4 Pages: 678-690
  • DOI: 10.1093/jrr/rrv024
  • Peer Reviewed / Open Access
• [Journal Article] LW6, a hypoxia-inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells. (2015)
  • Author(s): M. Sato , K. Hirose , I. Kashiwakura , M. Aoki , H. Kawaguchi , Y. Hatayama , H. Akimoto , Y. Narita , Y. Takai.
  • Journal Title: Molecular Medicine Reports Volume: 2(3) Issue: 3 Pages: 3462-3468
  • DOI: 10.3892/mmr.2015.3862
  • Peer Reviewed / Open Access
• [Journal Article] Mitigative Effects of a Combination of Multiple Pharmaceutical Drugs on the Survival of Mice Exposed to Lethal Ionizing Radiation. (2015)
  • Author(s): T. Hirouchi, K. Ito, M. Nakano, S. Monzen, H. Yoshino, M. Chiba, M. Hazawa, A. Nakano, J. Ishikawa, M. Yamaguchi, K. Tanaka, I. Kashiwakura.
  • Journal Title: Current Pharmaceutical Biotechnology Volume: 17(2) Pages: 190-199
  • Peer Reviewed
• [Journal Article] Effects of ionizing radiation on differentiation of murine bone marrow cells into mast cells. (2015)
  • Author(s): S. Murakami , H. Yoshino , J. Ishikawa, M. Yamaguchi , T. Tsujiguchi , A. Nishiyama , K. Yokoyama , I. Kashiwakura .
  • Journal Title: Journal of Radiation Research Volume: 56(6) Issue: 6 Pages: 865-871
  • DOI: 10.1093/jrr/rrv061
  • Peer Reviewed / Open Access
• [Presentation] 高線量放射線ばく露マウス血清中のmicroRNA 発現変化の被ばくマーカーとしての可能性の検討． (2016)
  • Author(s): 三浦柊太, 伊藤優樹, 山口平, 千葉満, 柏倉幾郎．
  • Organizer: 日本放射線影響学会第59回大会
  • Place of Presentation: ＪＭＳアステールプラザ（広島県広島市）
  • Year and Date: 2016-10-26
• [Presentation] 致死線量放射線ばく露マウスに対するトロンボポエチン受容体作動薬の放射線緩和効果． (2016)
  • Author(s): 山口平, 廣内篤久, 横山昂生, 千葉満, 小村潤一郎, 柏倉幾郎．
  • Organizer: 日本放射線影響学会第59回大会
  • Place of Presentation: ＪＭＳアステールプラザ（広島県広島市）
  • Year and Date: 2016-10-26
• [Presentation] 低線量γ線照射による細胞遺伝学的線量評価用線量応答曲線の作製. (2016)
  • Author(s): 阿部悠, 三浦富智, 吉田光明, 氏家里紗, 黒須由美子, 柳亜希，津山尚宏, 川村文彦, 藤岡来実, 稲葉俊哉, 神谷研二，坂井晃.
  • Organizer: 日本放射線影響学会第59回大会
  • Place of Presentation: ＪＭＳアステールプラザ（広島県広島市）
  • Year and Date: 2016-10-26
• [Presentation] 放射線によるToll様受容体の細胞表面発現制御機構の探索 (2016)
  • Author(s): 吉野浩教
  • Organizer: 日本放射線影響学会第59回大会
  • Place of Presentation: ＪＭＳアステールプラザ（広島県広島市）
  • Year and Date: 2016-10-26
• [Presentation] The mitigative effects of Romiplostim,a recombinant c-mpl agonist, on the surivival of mice exposed to lethal ionizing radiation. (2016)
  • Author(s): Yamaguchi M, Yokoyama K, Ito Y, Miura S, Chiba M, Kashiwakura I.
  • Organizer: The 3rd Educational Symposium on Radiation and Health by young scientists
  • Place of Presentation: 北海道大学（北海道札幌市）
  • Year and Date: 2016-10-01
  • Int'l Joint Research
• [Presentation] Thrombopoietin-Mimetic Romiplostim Confers the Complete Survival Rate to Mice Exposed to Lethal Ionizing Radiation. (2015)
  • Author(s): M. Yamaguchi, T. Hirouchi, M. Chiba, S. Monzen, H. Yoshino, J. Ishikawa, T. Tsujiguchi, A. Nishiyama, S. Murakami, J. Komura, I. Kashiwakura.
  • Organizer: 57th American Society of Hematology (ASH2015)
  • Place of Presentation: Orlande, USA.
  • Year and Date: 2015-12-05
  • Int'l Joint Research
• [Presentation] 致死線量放射線ばく露マウスに対するc-mpl作動薬の作用. (2015)
  • Author(s): 山口 平, 廣内 篤久, 千葉 満, 門前 暁, 吉野 浩教, 小村 潤一郎, 柏倉 幾郎.
  • Organizer: 日本放射線影響学会第1回放射線ワークショップ-未来に繋ぐ放射線研究-
  • Place of Presentation: 富山大学五福キャンパス黒田講堂（富山県富山市）
  • Year and Date: 2015-10-16
• [Presentation] エルトロンボパグの放射線防護効果の探索. (2015)
  • Author(s): 横山 昂生, 山口 平, 辻口 貴清, 柏倉 幾郎.
  • Organizer: 日本放射線影響学会第1回放射線ワークショップ-未来に繋ぐ放射線研究-
  • Place of Presentation: 富山大学五福キャンパス黒田講堂（富山県富山市）
  • Year and Date: 2015-10-16
• [Presentation] RIG-I様受容体アゴニストと放射線の併用による抗腫瘍効果増強． (2015)
  • Author(s): 吉野 浩教, 柏倉 幾郎.
  • Organizer: 日本放射線影響学会第1回放射線ワークショップ-未来に繋ぐ放射線研究-
  • Place of Presentation: 富山大学五福キャンパス黒田講堂（富山県富山市）
  • Year and Date: 2015-10-16
• [Presentation] Effects of a c-mpl agonist on mice exposed to lethal ionizing radiation. (2015)
  • Author(s): M. Yamaguchi, T. Hirouchi, M. Chiba, S. Monzen, H. Yoshino, J. Ishikawa, T. Tsujiguchi, A. Nishiyama, S. Murakami, J. Komura, I. Kashiwakura.
  • Organizer: 15th International Congress of Radiation Research (ICRR)
  • Place of Presentation: 京都国際会館（京都府京都市）
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] Expression analysis of c-Myc in bone marrow cells of mice exposed to ionizing radiation. (2015)
  • Author(s): K. Yokoyama, A. Nishiyama, T. Tsujiguchi, S. Murakami, M. Yamaguchi, I. Kashiwakura.
  • Organizer: 15th International Congress of Radiation Research (ICRR)
  • Place of Presentation: 京都国際会館（京都府京都市）
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] Up-regulated and Down-regulated Cis-natural Antisense Transcripts in the Human B Lymphoblastic Cells after X-ray Irradiation. (2015)
  • Author(s): M. Chiba, S. Monzen, I. Kashiwakura, T.Nakamura.
  • Organizer: 15th International Congress of Radiation Research (ICRR)
  • Place of Presentation: 京都国際会館（京都府京都市）
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] Effects of a c-mpl agonist on mice exposed to lethal ionizing radiation. (2015)
  • Author(s): M. Yamaguchi, T. Hirouchi, M. Chiba, S. Monzen, H. Yoshino, J. Ishikawa, T. Tsujiguchi, A. Nishiyama, S. Murakami, J. Komura, I. Kashiwakura.
  • Organizer: 2st Educational Symposium on Radiation and Health by young scientists (ESRAH2015)
  • Place of Presentation: 弘前大学保健学研究科（青森県弘前市）
  • Year and Date: 2015-05-23
  • Int'l Joint Research
• [Presentation] Expression analysis of c-Myc in bone marrow cells of mice exposed to ionizing radiation. (2015)
  • Author(s): K. Yokoyama, A. Nishiyama, T. Tsujiguchi, S. Murakami, M. Yamaguchi, I. Kashiwakura.
  • Organizer: 2st Educational Symposium on Radiation and Health by young scientists (ESRAH2015)
  • Place of Presentation: 弘前大学保健学研究科（青森県弘前市）
  • Year and Date: 2015-05-23
  • Int'l Joint Research
• [Presentation] Serum MicroRNAs as Potential Biomarkers in Mice Exposed to Ionizing Radiation. (2015)
  • Author(s): M. Chiba, S. Monzen, I. Kashiwakura, T.Nakamura.
  • Organizer: 2st Educational Symposium on Radiation and Health by young scientists (ESRAH2015)
  • Place of Presentation: 弘前大学保健学研究科（青森県弘前市）
  • Year and Date: 2015-05-23
  • Int'l Joint Research
• [Remarks] 弘前大学 大学院 柏倉研究室
  • URL: http://www.hs.hirosaki-u.ac.jp/~kashiwakura/
• [Remarks] 弘前大学大学院柏倉研究室
  • URL: http://www.hs.hirosaki-u.ac.jp/~kashiwakura/