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2018 年度 実績報告書

脳発達における細胞膜および核内ホルモン受容体の相互作用と環境化学物質による修飾

研究課題

研究課題/領域番号 18J23449
研究機関群馬大学

研究代表者

アリヤニ ウィンダ  群馬大学, 大学院医学系研究科, 特別研究員(DC1)

研究期間 (年度) 2018-04-25 – 2021-03-31
キーワードThyroid hormone / non-genomic / migration / proliferation / integrin
研究実績の概要

Thyroid hormones (THs) are known can bind to integrin αVβ3 and induces non-genomic pathway that involved on cell proliferation and migration. The purpose of this study is to investigate non-genomic effects of THs during cell proliferation and migration. I found that TH derivate (T3, T4, rT3, Triac and Tetrac) induced cell proliferation and migration in astrocyte cells, these effects were suppressed by cyclo-RGD (an integrin αVβ3 inhibitor). THs derivate also induced the phosphorylation of ERK1/2, Akt, and mTOR. THs also activate F-actin activity and cortical F-actin score index. This results indicate that the effect was mediated through integrin αVβ3 pathway, at least in part. In addition, I also examined the effects of environmental chemicals such as gadolinium (gadolinium-based contrast agents) on cell proliferation and migration in C6, glioma and Neuro-2A, neuroblastoma cell line. I also examined the effects of soybean isoflavone (genistein, daidzein, and S-Equol) on cerebellar development by primary cerebellar culture of Purkinje cells through the thyroid hormone receptor action. Now I also have one manuscript in preparation about the effects of S-Equol on cerebellar development.

現在までの達成度 (区分)
現在までの達成度 (区分)

2: おおむね順調に進展している

理由

This this project was runs according to the deadline of the proposal. I have completed all the basic physiological experiments about the non-genomics effects of thyroid hormones on the cell proliferation and migration. Next I will continue to investigate the mechanism of thyroid hormone induced cell migration through the F-actin modulation.

今後の研究の推進方策

This year I plan to clarify the mechanism thyroid hormone-induced cell migration through the F-actin modulation. I planned to examined the short exposure of thyroid hormone on cell migration and also examined the effects after knockdown of thyroid hormone receptor. Next I will continue to find the mechanism by measure the protein expression level with western blot for Rho-GTPase cascade including RhoA, RhoB, RhoC, Rac1/2/3, and cdc42 to clarify the modulation of F-actin by thyroid hormone.

  • 研究成果

    (4件)

すべて 2019 2018

すべて 雑誌論文 (2件) (うち国際共著 2件、 査読あり 2件) 学会発表 (2件) (うち国際学会 2件)

  • [雑誌論文] The Effects of Gadolinium-Based Contrast Agents on the Cerebellum: from Basic Research to Neurological Practice and from Pregnancy to Adulthood2018

    • 著者名/発表者名
      Ariyani Winda、Khairinisa Miski Aghnia、Perrotta Gaetano、Manto Mario、Koibuchi Noriyuki
    • 雑誌名

      The Cerebellum

      巻: 17 ページ: 247~251

    • DOI

      https://doi.org/10.1007/s12311-017-0903-4

    • 査読あり / 国際共著
  • [雑誌論文] A Possible Novel Mechanism of Action of Genistein and Daidzein for Activating Thyroid Hormone Receptor-Mediated Transcription2018

    • 著者名/発表者名
      Ariyani Winda、Iwasaki Toshiharu、Miyazaki Wataru、Yu Lu、Takeda Shigeki、Koibuchi Noriyuki
    • 雑誌名

      Toxicological Sciences

      巻: 164 ページ: 417~427

    • DOI

      https://doi.org/10.1093/toxsci/kfy097

    • 査読あり / 国際共著
  • [学会発表] Genistein and daidzein augments thyroid hormone-mediated dendritogenesis of cerebellar Purkinje cell.2019

    • 著者名/発表者名
      Winda Ariyani, Toshiharu Iwasaki, Wataru Miyazaki, Lu Yu, Shigeki Takeda, Noriyuki Koibuchi.
    • 学会等名
      9th Federation of the Asian and Oceanian Physiological Society (FAOPS2019)
    • 国際学会
  • [学会発表] Genistein and daidzein induces thyroid hormone-mediated dendritogenesis of cerebellar Purkinje cell via nuclear thyroid hormone receptor.2018

    • 著者名/発表者名
      Winda Ariyani, Toshiharu Iwasaki, Wataru Miyazaki, Lu Yu, Shigeki Takeda, Noriyuki Koibuchi.
    • 学会等名
      27th International Physiology Seminar
    • 国際学会

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公開日: 2019-12-27  

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