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2019 Fiscal Year Annual Research Report

Low operation by siRNA with angiogenetic inductive action and modal nano drug delivery, initiation of hurt repairing procedure

Research Project

Project/Area Number 17H02111
Research InstitutionSaga University

Principal Investigator

寺本 憲功  佐賀大学, その他部局等, 理事 (40294912)

Co-Investigator(Kenkyū-buntansha) 稲井 哲一朗  福岡歯科大学, 口腔歯学部, 教授 (00264044)
小玉 哲也  東北大学, 医工学研究科, 教授 (40271986)
山本 格士  佐賀大学, 医学部, 助教 (80762187)
Project Period (FY) 2017-04-01 – 2020-03-31
Keywordsナノ医工学 / 核酸医薬品 / 血管新生 / 創傷治癒
Outline of Annual Research Achievements

本研究は、『血管新生に深く関与する低酸素誘導因子(HIF-2α: Hypoxia-Induced Factor-2α)を特異的に抑制する制御因子(Int6)』を標的とし、これまでに 全く無い新しい設計理論に基づいて作成した核酸医薬、『RNA/DNA キメラ型siRNA』を『ハイブリッド型ナノバブル』中に封入し、『ソノポレーション法(音響穿 孔法)』を用い、皮膚や粘膜の創傷部周辺へ低侵襲的に本siRNAを導入し、新生微小血管を誘導させ、その結果、新たに形成された微小血行路を介して皮膚や粘膜の創傷治癒が促進されるか、否かについて遺伝子、組織および動物個体レベルで解析し、創傷治癒の期間の大幅な短縮化を目指す、これまでに無い画期的な低侵 襲性創傷治癒法の創成を研究目的とする。すなわち、本研究は“安心”かつ“安全”な創傷修復の促進を具現化する基礎的研究である。
ソノポレーション法を用いて様々な塩基配列の次世代型 siRNA を培養細胞(マウス骨格筋培養細胞)導入し、経時的かつ定量的に観察し、解析した。本次世代型siRNAを導入前(コントロール)および導入後の各一定時間(3 時間、6時間、12時間、24時間 、48時間)の後、培養細胞を採取し、本次世代型siRNA によるInt6 の選択的ノックダウン効果を遺伝子(real-time PCR法)およびタンパク質レベル(Western blotting法)で比較・検証した。また同様に血管新生関連因子群(Angiopoetin 1、VEGF、bFGF 等)の発現量の増減についても同様に本次世代型siRNAの導入前後にて遺伝子およびタンパク質レベルで解析した。

Research Progress Status

令和元年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和元年度が最終年度であるため、記入しない。

  • Research Products

    (12 results)

All 2019 Other

All Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 11 results) Remarks (1 results)

  • [Journal Article] Rab8a is involved in membrane trafficking of Kir6.2 in the MIN6 insulinoma cell line.2019

    • Author(s)
      Uchida K, Nomura M, Yamamoto T, Ogawa Y, TERAMOTO N
    • Journal Title

      Pflugers Archiv European Journal of Physiology

      Volume: 471 Pages: 877-887

    • DOI

      doi: 10.1007/s00424-018-02252-1

    • Peer Reviewed
  • [Journal Article] Serum affects keratinization and tight junctions in three-dimensional cultures of the mouse keratinocyte cell line COCA through retinoic acid receptor-mediated signaling.2019

    • Author(s)
      Ozaki A, Otani T, Kitagawa N, Ogata K, Iida H, Kojima H, Inai T.
    • Journal Title

      Histochemistry and Cell Biology

      Volume: 151 Pages: 315-326

    • DOI

      doi: 10.1007/s00418-018-1741-2

    • Peer Reviewed
  • [Journal Article] Anisomycin, a JNK and p38 activator, suppresses cell-cell junction formation in 2D cultures of K38 mouse keratinocyte cells and reduces claudin-7 expression, with an increase of paracellular permeability in 3D cultures.2019

    • Author(s)
      Nikaido M, Otani T, Kitagawa N, Ogata K, Iida H, Anan H, Inai T
    • Journal Title

      Histochemistry and Cell Biology

      Volume: 151 Pages: 369-384

    • DOI

      10.1007/s00418-018-1736-z

    • Peer Reviewed
  • [Journal Article] The reduced susceptibility of mouse keratinocytes to retinoic acid may be involved in the keratinization of oral and esophageal mucosal epithelium.2019

    • Author(s)
      Miyazono S, Otani T, Ogata K, Kitagawa N, Iida H, Inai Y, Matsuura T, Inai T
    • Journal Title

      Histochemistry and Cell Biology

      Volume: 153 Pages: 225-237

    • DOI

      10.1007/s00418-020-01845-1

    • Peer Reviewed
  • [Journal Article] A model system for studying superselective radiotherapy of lymph node metastasis in mice with swollen lymph nodes.2019

    • Author(s)
      Kikuchi R, Sukhbaatar A, Sakamoto M, Mori S, Kodama T
    • Journal Title

      Clinical and Translational Radiation Oncology

      Volume: 20 Pages: 53-57

    • DOI

      10.1016/j.ctro.2019.05.002

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Treatment of false-negative metastatic lymph nodes by a lymphatic drug delivery system with 5-fluorouracil.2019

    • Author(s)
      Fujii H, Horie S, Sukhbaatar A, Mishra R, Sakamoto M, Mori S, Kodama T
    • Journal Title

      Cancer Medicine

      Volume: 8 Pages: 2241-2251

    • DOI

      10.1002/cam4.2125

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The effect of anti-IL-6 receptor antibody for the treatment of McH-lpr/lpr-RA1 mice that spontaneously developed destructive arthritis and enthesitis.2019

    • Author(s)
      Izumiyama T, Mori Y, Mori S, Mori N, Kodama T, Itoi E
    • Journal Title

      BMC Musculoskeletal Disorders

      Volume: 20 Pages: 286-

    • DOI

      10.1186/s12891-019-2664-3

    • Peer Reviewed
  • [Journal Article] Electron holography on Fraunhofer diffraction.2019

    • Author(s)
      Harada K, Niitsu K, Shimada K, Kodama T, Akashi T, Ono YA, Shindo D, Shinada H, Mori S.
    • Journal Title

      Microscopy

      Volume: 68 Pages: 254-260

    • DOI

      10.1093/jmicro/dfz007

    • Peer Reviewed
  • [Journal Article] Use of a lymphatic drug delivery system and sonoporation to target malignant metastatic breast cancer cells proliferating in the marginal sinuses.2019

    • Author(s)
      Kato S, Shirai Y, Sakamoto M, Mori S, Kodama T
    • Journal Title

      Scientific Reports

      Volume: 13 Pages: 13242-

    • DOI

      10.1038/s41598-019-49386-5

    • Peer Reviewed
  • [Journal Article] Imaging of the mouse lymphatic sinus during early stage lymph node metastasis using intranodal lymphangiography with X-ray micro-computed tomography.2019

    • Author(s)
      Iwamura R, Sakamoto M, Mori S, Kodama T
    • Journal Title

      Molecular Imaging and Biology

      Volume: 21 Pages: 825-834

    • DOI

      10.1007/s11307-018-01303-4

    • Peer Reviewed
  • [Journal Article] Analysis of tumor vascularization in a mouse model of metastatic lung cancer.2019

    • Author(s)
      Sukhbaatar A, Sakamoto M, Mori S, Kodama T
    • Journal Title

      Scientific Reports

      Volume: 9 Pages: 16029-

    • DOI

      10.1038/s41598-019-52144-2

    • Peer Reviewed / Int'l Joint Research
  • [Remarks] 佐賀大学医学部薬理学

    • URL

      http://www.pharmacology.med.saga-u.ac.jp/YAKURIHP/Top_Page.html

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Published: 2021-01-27  

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