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2016 Fiscal Year Annual Research Report

Integrative studies on the dynamism of mesenchymal cells during tissue restoration/regeneration

Research Project

Project/Area Number 25221205
Research InstitutionThe University of Tokyo

Principal Investigator

尾崎 博  東京大学, 大学院農学生命科学研究科(農学部), 教授 (30134505)

Co-Investigator(Kenkyū-buntansha) 堀 正敏  東京大学, 大学院農学生命科学研究科(農学部), 准教授 (70211547)
日下部 守昭  東京大学, 大学院農学生命科学研究科(農学部), 特任教授 (60153277)
池田 正浩  宮崎大学, 農学部, 教授 (60281218)
飯野 哲  福井大学, 学術研究院医学系部門, 教授 (40242854)
堀口 和秀  福井大学, 学術研究院医学系部門, 准教授 (20377451)
下島 直樹  慶應義塾大学, 医学部(信濃町), 講師 (30317151)
Project Period (FY) 2013-05-31 – 2017-03-31
Keywords間葉系細胞 / 筋線維芽細胞 / 平滑筋細胞 / 上皮細胞 / 内皮細胞 / 組織修復・再生 / 炎症 / 細胞運動
Outline of Annual Research Achievements

中間評価コメントで、疾病治療を意識した研究に進展すべきという指摘を受けたことから、これを意識しつつ研究を継続した。論文発表に至った主な業績を以下に記す。
①カハール介在細胞は消化管運動のペースメーカーを担う細胞であり、炎症病態時の運動機能低下にその変化がどのように関わるかかについての研究は重要である。本研究では、腸管微小クラスター標本を用い、機能低下の分子メカニズム(IFNgとLPSによる誘導型NO産生酵素iNOSの発現)を解明した。(Pharmacol Res. 2016 111:838-848)(IF:4.816)
②IL-33は不明な点の多い新規炎症性サイトカインである。消化管炎症における役割について、上皮細胞における産生能に焦点をあて研究を行った。上皮細胞が炎症時にIL-33を産生すること、EMT変換に伴い分泌されるEGFがそのメディエーターであること、EGF受容体であるST2の発現も上昇させること等を明らかにした。(Br J Pharmacol. 2016 173(16):2532-2542)(IF:5.259).
③腎線維化に伴うバイオマーカー研究として、今話題となっているエクソソームに着目して虚血再潅流腎障害モデルを用い検討し、尿中エクソソームに排出される水チャネル(aquaporin1,2)の有用性を明らかにした。(Nephrology Dialysis Transplantation, 2016, 31, 1623-1632, IF:4.085; Am J Physiol, 2017, 印刷中, IF:3.611)
④繰越し申請の理由とした脱リン酸化阻害因子CPI-17の機能研究についても、2報の論文を公表出来た。(FASEB J. 2018 32(4):2095-2109, IF:5.498; J Vet Med Sci, IF:0.845)

Research Progress Status

28年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

28年度が最終年度であるため、記入しない。

  • Research Products

    (32 results)

All 2018 2017 2016 Other

All Journal Article (18 results) (of which Peer Reviewed: 18 results) Presentation (13 results) (of which Int'l Joint Research: 4 results,  Invited: 6 results) Remarks (1 results)

  • [Journal Article] Characterization of urinary exosomal release of aquaporin-1 and -2 after renal ischemia-reperfusion in rats2018

    • Author(s)
      Asvapromtada S, Sonoda H, Kinouchi M, Oshikawa S, Takahashi S, Hoshino Y, Sinlapadeelerdkul T, Yokota-Ikeda N, Matsuzaki T, Ikeda M
    • Journal Title

      Am J Physiol Renal Physiol

      Volume: 314(4) Pages: F584-F601

    • DOI

      doi: 10.1152/ajprenal.00184.2017.

    • Peer Reviewed
  • [Journal Article] Disruption of the pacemaker activity of interstitial cells of Cajal via nitric oxide contributes to postoperative ileus2018

    • Author(s)
      Kaji N, Nakayama S, Horiguchi K, Iino S, Ozaki H, Hori M
    • Journal Title

      Neurogastroenterol Motil

      Volume: 15 Pages: 印刷中

    • DOI

      10.1111/nmo.13334.

    • Peer Reviewed
  • [Journal Article] Inhibition of actin polymerization by marine toxin pectenotoxin-22018

    • Author(s)
      Hori M, Yazama F, Matsuura Y, Yoshimoto R, Kaneda T, Yasumoto T, Ozaki H, Karaki H
    • Journal Title

      J Vet Med Sci

      Volume: 9;80(2) Pages: 225-234

    • DOI

      10.1292/jvms.17-0654.

    • Peer Reviewed
  • [Journal Article] Angiotensin II, a unique vasoactive agent dissociates myosin light chain phosphorylation from contraction2018

    • Author(s)
      Hirano T, Kaneda T, Ozaki H, Hori M
    • Journal Title

      J Vet Med Sci

      Volume: 9;80(2) Pages: 219-224

    • DOI

      10.1292/jvms.17-0415.

    • Peer Reviewed
  • [Journal Article] Induction of myosin light chain kinase and CPI-17 by TGF-b accelerates contractile activity in intestinal epithelial cells2018

    • Author(s)
      Md. Shafiqul Islam, Kaji N, Mikawa S, Yang Q, Kusabe M, Hori M, Ozaki H
    • Journal Title

      J Vet Med Sci

      Volume: 印刷中 Pages: 印刷中

    • DOI

      in press

    • Peer Reviewed
  • [Journal Article] Oral administration with diosgenin enhances the induction of intestinal T helper 1-like regulatory T cells in a murine model of food allergy2017

    • Author(s)
      Huang C-H, Wang C-C, Lind Y-J, Hori M, Jan T-R
    • Journal Title

      Int Immunopharmacol

      Volume: 42 Pages: 59-66

    • DOI

      10.1016/j.intimp.2016.11.021.

    • Peer Reviewed
  • [Journal Article] Micro-coordination of pacemaker potentials in the intestine of the mouse Gastroenterology in Motion (2017)2017

    • Author(s)
      Morishita H, Noda T, Mochizuki N, Kaji N, Hori M, Kajioka S, Nakayama S
    • Journal Title

      Gastroenterology

      Volume: 152(8) Pages: 1831-1833

    • DOI

      10.1053/j.gastro.2017.04.016

    • Peer Reviewed
  • [Journal Article] The essential role of phospho-T38 CPI-17 in the maintenance of physiological blood pressure using genetically modified mice2017

    • Author(s)
      Yang Q, Fujii W, Kaji N, Kakuta S, Kada K, Kuwahara M, Tsubone H, Ozaki H, Hori M
    • Journal Title

      FASEB J

      Volume: 32(4) Pages: 2095-2109

    • DOI

      10.1096/fj.201700794R

    • Peer Reviewed
  • [Journal Article] The anti-inflammatory pathway regulated via nicotinic acetylcholine receptors in rat intestinal mesothelial cells2017

    • Author(s)
      Mihara T, Otsubo W, Horiguchi K, Mikawa S, Kaji N, Iino S, Ozaki H, Hori M
    • Journal Title

      J Vet Med Sci

      Volume: 10;79(11) Pages: 1795-1802

    • DOI

      10.1292/jvms.17-0304.

    • Peer Reviewed
  • [Journal Article] Therapeutic Action of Honokiol on Postoperative Ileus via Downregulation of iNOS Gene Expression2017

    • Author(s)
      Mihara T, Mikawa S, Kaji N, Endo M, Oikawa T, Tong-Rong J, Ozaki H, Hori M. Inflammation
    • Journal Title

      Inflammation

      Volume: 40(4) Pages: 1331-1341

    • DOI

      10.1007/s10753-017-0576-7.

    • Peer Reviewed
  • [Journal Article] Zingiberis Siccatum Rhizoma, the active component of the Kampo formula Daikenchuto, induces anti-inflammatory actions through α7 nicotinic acetylcholine receptor activation2017

    • Author(s)
      Endo M, Hori M, Mihara T, Ozaki H, Oikawa T, Odaguchi H, Hanawa T
    • Journal Title

      Neurogastroenterol Motil

      Volume: 29(12) Pages: e13139

    • DOI

      doi: 10.1111/nmo.13139.

    • Peer Reviewed
  • [Journal Article] Comprehensive DNA microarray expression profiles of tumors in tenascin-C-knockout mice2017

    • Author(s)
      Matsumoto K, Nakai Y, Hoshino M, Yamazaki K, Takioto Y, Takadera S, Nakagawa T, Nishimura R, Kusakabe M
    • Journal Title

      Biosci Biotechnol Biochem

      Volume: 81(10) Pages: 1926-1936

    • DOI

      10.1080/09168451.2017.1362975.

    • Peer Reviewed
  • [Journal Article] Nitric oxide-induced oxidative stress impairs pacemaker function of murine interstitial cells of Cajal during inflammation2016

    • Author(s)
      Kaji N, Horiguchi K, Iino S, Nakayama S, Ohwada T, Otani Y, Firman, Murata T, Sanders KM, Ozaki H, Hori M.
    • Journal Title

      Pharmacol Res

      Volume: 111 Pages: 838-48

    • DOI

      10.1016/j.phrs.2016.07.030.

    • Peer Reviewed
  • [Journal Article] Epidermal growth factor is a critical regulator of the cytokine IL-33 in intestinal epithelial cells2016

    • Author(s)
      Islam MS, Horiguchi K, Iino S, Kaji N, Mikawa S, Hori M, Ozaki H.
    • Journal Title

      Br J Pharmacol

      Volume: 173(16) Pages: 2532-42

    • DOI

      10.1111/bph.13535.

    • Peer Reviewed
  • [Journal Article] Acetazolamide enhances the release of urinary exosomal aquaporin-12016

    • Author(s)
      Abdeen A, Sonoda H, Oshikawa S, Hoshino Y, Kondo H, Ikeda M
    • Journal Title

      Nephrol Dial Transplant

      Volume: 31(10) Pages: 1623-32

    • DOI

      10.1093/ndt/gfw033.

    • Peer Reviewed
  • [Journal Article] Aquaporins in Urinary Extracellular Vesicles (Exosomes)2016

    • Author(s)
      Oshikawa S, Sonoda H, Ikeda M
    • Journal Title

      Int J Mol Sci

      Volume: 17(6) Pages: pii: E957

    • DOI

      10.3390/ijms17060957

    • Peer Reviewed
  • [Journal Article] Fluorescence Visualization of the Enteric Nervous Network in a Chemically Induced Aganglionosis Model2016

    • Author(s)
      Fujimura T, Shibata S, Shimojima N, Morikawa Y, Okano H, Kuroda T
    • Journal Title

      PLoS One

      Volume: 11(3) Pages: e0150579

    • DOI

      10.1371/journal.pone.0150579.

    • Peer Reviewed
  • [Journal Article] The optimal immunosuppressive protocol for the portal vein infusion of PGE1 and methylprednisolone in pediatric liver transplantation for fulminant hepatic failure of unknown etiology2016

    • Author(s)
      Yamada Y, Hoshino K, Irie R, Tomita H, Kato M, Shimojima N, Fujino A, Hibi T, Shinoda M, Obara H, Itano O, Kawachi S, Tanabe M, Sakamoto M, Kitagawa Y, Kuroda T
    • Journal Title

      Pediatr Transplant

      Volume: 20(5) Pages: 640-6

    • DOI

      10.3390/ijms17060957

    • Peer Reviewed
  • [Presentation] Proof of importance of phospho-CPI-17 at Thr38 in maintenance of normotensive pressure using genetically modified mice2018

    • Author(s)
      Hori M
    • Organizer
      第95回 日本生理学会
    • Invited
  • [Presentation] Neural anti-inflammatory action mediated through two types of ACh receptors of small intestine in POI model mice. For Mosapride citrate2017

    • Author(s)
      Hori M
    • Organizer
      ANMA & JSNM Joint Meeting 2017 (5th Biennial Congress of the Asian Neurogastroenterology & Motility Association (ANMA) and 19th Japanese Society of Neurogastroenterology and Motility (JSNM))
    • Int'l Joint Research / Invited
  • [Presentation] CPI-17ノックアウトマウスを用いた気管支平滑筋の収縮におけるCPI-17の機能解析2017

    • Author(s)
      加田 浩大、 Qunhui Yang、 梶 典幸、 尾崎 博、 堀 正敏
    • Organizer
      第59回日本平滑筋学会
    • Invited
  • [Presentation] 5-フルオロウラシルによる腸管上皮細胞のアポトーシスはセロトニン3A受容体シグナルを介して増強される2017

    • Author(s)
      三河 翔馬、梶 典幸、三原 大輝、尾崎 博、堀 正敏
    • Organizer
      第137回日本薬理学会関東部会
  • [Presentation] Pathogenic role of P2X7 in postoperative ileus2017

    • Author(s)
      Yamazaki T, Mikawa S, Kaji N, Ozaki H, Hori M
    • Organizer
      The 90th Annual Meeting of the Japanese Pharmacological Society
    • Invited
  • [Presentation] The importance of intestinal macrophages for the anti-inflammatory action mediated by α7nAChR on postoperative ileus2017

    • Author(s)
      Nakashima J, Mihara T, Kaji N, Ozaki H, Hori M
    • Organizer
      The 90th Annual Meeting of the Japanese Pharmacological Society
  • [Presentation] 消化器疾患の薬物治療2017

    • Author(s)
      堀 正敏
    • Organizer
      平成28年度日本獣医師会 獣医学術学会年次大会
    • Invited
  • [Presentation] c-Kitシグナル異常を持つマウスにおける小腸カハール介在細胞の発生2017

    • Author(s)
      飯野哲、堀口里美、堀口和秀、橋本隆
    • Organizer
      日本顕微鏡学会 第73回学術講演会
  • [Presentation] TNBS腸炎モデルマウスを用いた結腸筋層の傷害と回復過程研究2017

    • Author(s)
      飯野哲、堀口和秀、堀口里美、橋本隆、川原真代、杉本京平
    • Organizer
      第49回日本臨床分子形態学会総会・学術集会
  • [Presentation] The anti-inflammatory action of honokiol, a herbal medicinal product, on postoperative ileus2016

    • Author(s)
      Mihara T,Mikawa S, Kaji N, Jan T-R, Ozaki H and Hori M
    • Organizer
      The Joint Symposium of the 7th Veterinary Research among Universities of Veterinary Medicine in East Asia
    • Int'l Joint Research
  • [Presentation] Neural anti-inflammatory signaling via activating 5-HT4 receptor in gastrointestine2016

    • Author(s)
      Hori M
    • Organizer
      The Joint Symposium of the 7th Veterinary Research among Universities of Veterinary Medicine in East Asia
    • Int'l Joint Research / Invited
  • [Presentation] Th1 inflammatory signaling impairs pacemaker function of interstitial cells of Cajal through nitric oxide-induced oxidative stress2016

    • Author(s)
      Kaji N, Nakayama S, Horiguchi K, Iino S, Ozaki H and Hori M
    • Organizer
      The 89th Annual Meeting of the Japanese Pharmacological Society
  • [Presentation] The function of intestinal pacemaker cells is impaired by nitric oxide derived from resident macrophages and smooth muscle cells during Th1 inflammation2016

    • Author(s)
      Kaji N, Horiguchi K, Iino S, Nakayama S, Ozaki H and Hori M
    • Organizer
      The 24th International Symposium on Molecular Cell Biology of Macrophages (MMCB2016)
    • Int'l Joint Research
  • [Remarks] 組織再生・修復における間葉系細胞のダイナミズム

    • URL

      http://www.vm.a.u-tokyo.ac.jp/yakuri/kiban-s-new/index.html

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Published: 2018-12-17  

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