Analysis of mechanisms of overexpression of angiotensin converting enzyme and heart failure in transgenic mice of miRNAs

• Project/Area Number: 25460506
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Chubu University
• Principal Investigator: IWAMOTO Takashi 中部大学, 生命健康科学部, 教授 (60223426)
• Co-Investigator(Kenkyū-buntansha): ICHIHARA Masatoshi 中部大学, 生命健康科学部, 教授 (00314013) ; NODA Akiko 中部大学, 臨床検査技術教育・実習センター, 教授 (80252287)
• Co-Investigator(Renkei-kenkyūsha): OUCHI Yasuo 千葉大学, 大学院医学系研究科, 助教 (70553858) ; UEYAMA Tomomi 京都府立医科大学, 医学系研究科, 講師 (80379388)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: マイクロRNA / 拡張型心筋症 / アンジオテンシン変換酵素 / ヘキソキナーゼ２ / MAS1 / マイクロＲＮＡ / トランスジェニックマウス

Outline of Final Research Achievements

Dilated cardiomyopathy is one of the intractable diseases. microRNAs are small molecules, which were discovered around two decades ago, and have turned out to be involved in many human diseases. We generated the transgenic mice that expressed miR-143/145 in the heart muscles, and found that they died due to the human-like dilated cardiomyopathy.
The expression of angiotensin converting enzyme (ACE) increased in their hearts and ACE inhibitor significantly improved the condition of the mice. In addition, while ACE2 expression was also increased, the MAS1 receptor was clearly downregulated. These data imply that the dysregulation of key molecules of angiotensin metabolism might be involved in the pathology of these mice. Furthermore, we found that one glycolysis enzyme, hexokinase 2(HK2), was dramatically decreased in the hearts of the mice, and the expression of key molecules of autophagy was disturbed, suggesting the disorder of autophagy might be involved in this pathology.

Research Products

• [Int'l Joint Research] フロリダ大学(米国)
• [Journal Article] Pasteurella pneumotropica感染後の対応について－ソフト酸化水を使用したクリーニング操作の検討 (2016)
  • Author(s): 長原美樹，松永歩，藤田芳顕，上瀬茉美，石坂みゆき，上田潤，岩本隆司
  • Journal Title: 中部大学生命健康科学研究所紀要 Volume: 12 Pages: 92-95
  • NAID: 120006520510
  • Open Access
• [Journal Article] Simultaneous oral and inhalational intake of molecular hydrogen additively suppresses signaling pathways in rodents. (2015)
  • Author(s): Sobue S, Yamai K, Ito M, Ohno K, Ito M, Iwamoto T, Qiao S, Ohkuwa T, Ichihara M
  • Journal Title: Mol Cell Biochem. Volume: 403 Issue: 1-2 Pages: 231-241
  • DOI: 10.1007/s11010-015-2353-y
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Emerging evidence of insulin-like growth factor 2 as a memory enhancer: a unique animal model of cognitive dysfunction with impaired adult neurogenesis (2014)
  • Author(s): Iwamoto T, Ouchi Y.
  • Journal Title: Rev Neurosci. Volume: 25 Issue: 4 Pages: 559-574
  • DOI: 10.1515/revneuro-2014-0010
  • Peer Reviewed
• [Journal Article] The Heterochronic Genes lin-28a and lin-28b play an Essential and Evolutionarily Conserved Role in Early Zebrafish development. (2014)
  • Author(s): Ouchi Y, Yamamoto J, Iwamoto T
  • Journal Title: PLoS One Volume: 9 Issue: 2 Pages: 88086-88086
  • DOI: 10.1371/journal.pone.0088086
  • Peer Reviewed
• [Journal Article] G protein-coupled receptor 43 moderates gut inflammation through cytokine regulation from mononuclear cells. (2013)
  • Author(s): Masui R, Sasaki M, Funaki Y, Ogasawara N, Mizuno M, Iida A, Izawa S, Kondo Y, Ito Y, Tamura Y, Yanamoto K, Noda H, Tanabe A, Okaniwa N, Yamaguchi Y, Iwamoto T, Kasugai K.
  • Journal Title: Inflamm Bowel Dis Volume: 19 Issue: 13 Pages: 2848-2856
  • DOI: 10.1097/01.mib.0000435444.14860.ea
  • Peer Reviewed
• [Journal Article] Deficits in microRNA-mediated Cxcr4/Cxcl12 signaling in neurodevelopmental deficits in a 22q11 deletion syndrome mouse model. (2013)
  • Author(s): Toritsuka M, Kimoto S, Muraki K, Landek-Salgado MA, Yoshida A, Yamamoto N, Horiuchi Y, Hiyama H, Tajinda K, Keni N, Illingworth E, Iwamoto T, Kishimoto T, Sawa A, Tanigaki K.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 110 Issue: 43 Pages: 17552-17557
  • DOI: 10.1073/pnas.1312661110
  • Peer Reviewed
• [Journal Article] Reduced adult hippocampal neurogenesis and working memory deficits in the Dgcr8-deficient mouse model of 22q11.2 deletion-associated schizophrenia can be rescued by IGF2. (2013)
  • Author(s): Ouchi Y, Banno Y, Shimizu Y, Ando S, Hasegawa H, Adachi K, Iwamoto T
  • Journal Title: J Neurosci. Volume: 33 Issue: 22 Pages: 9408-9419
  • DOI: 10.1523/jneurosci.2700-12.2013
  • Peer Reviewed
• [Presentation] 心筋特異的miR-143トランスジェニックマウスではヘキソキナーゼ２発現低下と相関して拡張型心筋症が発症し、ACE阻害剤で改善する (2015)
  • Author(s): 岩本隆司 上田潤 高岡祐司 松山留美子 野田明子 喬善楼 上山知己 安達興一
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド、神戸市、兵庫県
  • Year and Date: 2015-12-01
• [Presentation] マウス精巣特異的ヒストンH3バリアントであるH3tは精子形成過程に必須である (2015)
  • Author(s): 上田潤 浦浜嵩 原田哲仁 他１４名 １０番目
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド、神戸市、兵庫県
  • Year and Date: 2015-12-01
• [Presentation] Mouse testis specific histone H3 variant, H3t is essential for spermatogenesis and ensures the entry into meiosis. (2015)
  • Author(s): Ueda, J., Urahama, T., Harada, A., Machida, S., Maehara, K., Horikoshi, N., Osakabe, A., Tachiwana, H., Yao, T., Iwamoto, T., Isotani, A., Ikawa, M., Tachibana, T., Kimura, H., Ohkawa, Y., Kurumizaka, H., and Yamagata, K.
  • Organizer: International Symposium ‘Non-coding DNA and Chromosomal Integrity’
  • Place of Presentation: Awaji Yumebutai International Conference Center, Awaji Island, Hyogo, Japan.
  • Year and Date: 2015-08-07
  • Int'l Joint Research
• [Presentation] マイクロRNAトランスジェニックマウスに発症する拡張型心筋症の解析 (2015)
  • Author(s): 岩本隆司 上田潤
  • Organizer: 第13回がんとハイポキシア研究会
  • Place of Presentation: 国立遺伝学研究所 、静岡県、三島市
  • Year and Date: 2015-06-05
• [Presentation] The Lin28/let-7 axis regulates intestinal epithelial cell proliferation and tumor formation (2013)
  • Author(s): Ouchi Y, Tsuruda H, Nakashima T, Takaoka Y, Asaeda Y, Iwamoto T
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド（神戸市)
• [Presentation] Reduced adult hippocampal neurogenesis and working memory deficits in the DGCR8-deficient mouse model of 22q11.2 deletion-associated schizophrenia can be rescued by IGF2 (2013)
  • Author(s): Banno Y, Ouchi Y, Hakumoto Y, Shimizu Y, Andou S, Adachi K, Iwamoto T
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド（神戸市)
• [Presentation] Deficiency of DGCR8 gene, a candidate gene for 22q11.2 deletion-associated schizophrenia, decreases cell proliferation and neurogenesis in the adult mouse dentate gyrus
  • Author(s): 大内靖夫, 坂野祐哉, 清水裕子, 安藤章太, 安達興一, 岩本隆司
  • Organizer: 第11回幹細胞シンポジウム
  • Place of Presentation: 東京大学（東京）
• [Remarks] 中部大学実験動物教育研究センター
  • URL: http://www3.chubu.ac.jp/celar/
• [Remarks] 中部大学・教員情報
  • URL: http://www.chubu.ac.jp/about/faculty/profile/6322fcf3ae47743e17deca4b73899194b102cfe7.html