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Elucidation of hepatocyte volume regulation and liver regeneration mechanism through TRPM2 activity.

Research Project

Project/Area Number 18K06864
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48020:Physiology-related
Research InstitutionFukuoka University

Principal Investigator

Numata Tomohiro  福岡大学, 医学部, 講師 (20455223)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords細胞容積調節能 / 細胞容積調節 / TRP / 肝臓 / 機械刺激 / イオンチャネル
Outline of Final Research Achievements

Among the mammalian organs, the liver is known to have a particularly high regenerative capacity. There are many unclear points at the cellular level regarding the extraordinary regeneration mechanism of hepatocytes. Therefore, the purpose of this study was to elucidate the molecular mechanism of activation of TRP that works in the process of increasing cell volume, its role in liver tissue, and the mechanism of regeneration from liver damage. This research project explored detailed cell proliferation, cell viability, and cell growth mechanism using cell lines and expression cells, further isolate hepatocytes and activate TRP and its peripheral molecules in individual cells. By exploring the molecular mechanism and measuring in situ cell volume in vivo using a newly developed technology, it was clarified that TRP is involved in the hepatocyte proliferation mechanism.

Academic Significance and Societal Importance of the Research Achievements

肝硬変、肝がんの患者数は日本で推定11万人が罹患しているといわれている(厚生労働省健康局資料, WHO2008)。肝炎ウイルス感染やアルコール多飲、脂肪沈着などが引き起こす肝硬変は、肝臓病が多い国民の健康を害する大きな要因の一つであるが、有効な治療法がない。そのために、本研究結果は肝細胞における細胞容積増大にTRPの活性化分子機構を解明したことで、これらの有効な再生を促す治療法の開発へ重要な基盤情報を与え、その発展に寄与することが期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (41 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (8 results) Journal Article (15 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 15 results,  Open Access: 12 results) Presentation (17 results) (of which Int'l Joint Research: 4 results) Remarks (1 results)

  • [Int'l Joint Research] University of Hawaii(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Leibniz-Forschungsinstitut/Max-Delbruck-Centrum(ドイツ)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] National University of Uzbekistan(ウズベキスタン)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] マックスプランク分子生理学研究所/労働生理学研究所(ドイツ)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] ハワイ大学(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Academy of Sciences of Uzbekistan(ウズベキスタン)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] China Medical University(中国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Max Planck Institute/ifado(ドイツ)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Cell Death Induction and Protection by Activation of Ubiquitously Expressed Anion/Cation Channels. Part 1: Roles of VSOR/VRAC in Cell Volume Regulation, Release of Double-Edged Signals and Apoptotic/Necrotic Cell Death2021

    • Author(s)
      Okada Yasunobu, Sabirov Ravshan Z., Sato-Numata Kaori, Numata Tomohiro
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 8 Pages: 614040-614040

    • DOI

      10.3389/fcell.2020.614040

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SGLT2 inhibitor ipragliflozin attenuates breast cancer cell proliferation2020

    • Author(s)
      Komatsu Shiho、Nomiyama Takashi、Numata Tomohiro、Kawanami Takako、Hamaguchi Yuriko、Iwaya Chikayo、Horikawa Tsuyoshi、Fujimura-Tanaka Yuki、Hamanoue Nobuya、Motonaga Ryoko、Tanabe Makito、Inoue Ryuji、Yanase Toshihiko、Kawanami Daiji
    • Journal Title

      Endocrine Journal

      Volume: 67 Issue: 1 Pages: 99-106

    • DOI

      10.1507/endocrj.EJ19-0428

    • NAID

      130007790952

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cryo-EM structure of the volume-regulated anion channel LRRC8D isoform identifies features important for substrate permeation2020

    • Author(s)
      Nakamura Ryoki、Numata Tomohiro、Kasuya Go、Yokoyama Takeshi、Nishizawa Tomohiro、Kusakizako Tsukasa、Kato Takafumi、Hagino Tatsuya、Dohmae Naoshi、Inoue Masato、Watanabe Kengo、Ichijo Hidenori、Kikkawa Masahide、Shirouzu Mikako、Jentsch Thomas J.、Ishitani Ryuichiro、Okada Yasunobu、Nureki Osamu
    • Journal Title

      Communications Biology

      Volume: 3 Issue: 1 Pages: 240-240

    • DOI

      10.1038/s42003-020-0951-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] O2-Dependent Protein Internalization Underlies Astrocytic Sensing of Acute Hypoxia by Restricting Multimodal TRPA1 Channel Responses2020

    • Author(s)
      Uchiyama Makoto、Nakao Akito、Kurita Yuki、Fukushi Isato、Takeda Kotaro、Numata Tomohiro、Tran Ha Nam、Sawamura Seishiro、Ebert Maximilian、Kurokawa Tatsuki、Sakaguchi Reiko、Stokes Alexander J.、Takahashi Nobuaki、Okada Yasumasa、Mori Yasuo
    • Journal Title

      Current Biology

      Volume: 30 Issue: 17 Pages: 3378-3396

    • DOI

      10.1016/j.cub.2020.06.047

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Elucidation of the Mechanisms for the Underlying Depolarization and Reversibility by Photoactive Molecule.2020

    • Author(s)
      Numata Tomohiro、Fukuda Ryosuke、Hirano Mitsuru、Yamaguchi Kazuma、Sato-Numata Kaori、Imahori Hiroshi、Murakami Tatsuya
    • Journal Title

      Cellular Physiology and Biochemistry

      Volume: 54 Issue: 5 Pages: 899-916

    • DOI

      10.33594/000000277

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression and functions of N-type Cav2.2 and T-type Cav3.1 channels in rat vasopressin neurons under normotonic conditions2020

    • Author(s)
      Sato-Numata Kaori, Numata Tomohiro, Ueta Yoichi, Okada Yasunobu
    • Journal Title

      The Journal of Physiological Sciences

      Volume: 70 Issue: 1 Pages: 49-49

    • DOI

      10.1186/s12576-020-00775-w

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TRPM7 channels mediate spontaneous Ca2+ fluctuations in growth plate chondrocytes that promote bone development.2019

    • Author(s)
      Qian N, Ichimura A, Takei D, Sakaguchi R, Kitani A, Nagaoka R, Tomizawa M, Miyazaki Y, Miyachi H, Numata T, Kakizawa S, Nishi M, Mori Y, Takeshima H.
    • Journal Title

      Science signaling

      Volume: 12 Issue: 576 Pages: 4847-4847

    • DOI

      10.1126/scisignal.aaw4847

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Herbal components of Japanese Kampo medicines exert laxative actions in colonic epithelium cells via activation of BK and CFTR channels2019

    • Author(s)
      Numata Tomohiro、Sato-Numata Kaori、Okada Yasunobu
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 15554-15554

    • DOI

      10.1038/s41598-019-52171-z

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] TRPM7 is involved in acid-induced necrotic cell death in a manner sensitive to progesterone in human cervical cancer cells2019

    • Author(s)
      Numata Tomohiro、Sato-Numata Kaori、Okada Yasunobu
    • Journal Title

      Physiological Reports

      Volume: 7 Issue: 13

    • DOI

      10.14814/phy2.14157

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Short TRPM2 prevents the targeting of full-length TRPM2 to the surface transmembrane by hijacking to ER associated degradation2019

    • Author(s)
      Yamamoto Shinichiro、Ishii Takahiro、Mikami Ryota、Numata Tomohiro、Shimizu Shunichi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 520 Issue: 3 Pages: 520-525

    • DOI

      10.1016/j.bbrc.2019.10.065

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Construction of a Fluorescent Screening System of Allosteric Modulators for the GABAAReceptor Using a Turn-On Probe2019

    • Author(s)
      Sakamoto Seiji、Yamaura Kei、Numata Tomohiro、Harada Fumio、Amaike Kazuma、Inoue Ryuji、Kiyonaka Shigeki、Hamachi Itaru
    • Journal Title

      ACS Central Science

      Volume: 5 Issue: 9 Pages: 1541-1553

    • DOI

      10.1021/acscentsci.9b00539

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cell Volume-Activated and -Correlated Anion Channels in Mammalian Cells: Their Biophysical, Molecular and Pharmacological Properties.2019

    • Author(s)
      Y. Okada, T. Okada, K.S. Numata, M.R. Islam, Y.A. Akatsuka, T. Numata, M. Kubo, T. Shimizu, R.S. Kurbannazarova, Y. Marunaka, and R.Z. Sabirov
    • Journal Title

      Pharmacological Reviews

      Volume: 71 Issue: 1 Pages: 49-88

    • DOI

      10.1124/pr.118.015917

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Roles of volume-regulatory anion channels, VSOR and Maxi-Cl, in apoptosis, cisplatin resistance, necrosis, ischemic cell death, stroke and myocardial infarction2019

    • Author(s)
      Yasunobu Okada, Tomohiro Numata, Kaori Sato-Numata, Ravshan Z. Sabirov, Hongtao Liu, Shin-ichiro Mori, and Shigeru Morishima
    • Journal Title

      Current Topics in Membranes

      Volume: 印刷中 Pages: 205-283

    • DOI

      10.1016/bs.ctm.2019.03.001

    • ISBN
      9780128177648
    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cellular mechanism for herbal medicine Junchoto to facilitate intestinal Cl-/water secretion that involves cAMP-dependent activation of CFTR2018

    • Author(s)
      Tomohiro Numata, Kaori Sato-Numata, Yasunobu Okada, Ryuji Inoue
    • Journal Title

      Journal of Natural Medicines

      Volume: 印刷中 Issue: 3 Pages: 694-705

    • DOI

      10.1007/s11418-018-1207-9

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] TRPM7-mediated spontaneous Ca2+ entry regulates the proliferation and differentiation of human leukemia cell line K5622018

    • Author(s)
      Takahashi Kiriko、Umebayashi Chisato、Numata Tomohiro、Honda Akira、Ichikawa Jun、Hu Yaopeng、Yamaura Ken、Inoue Ryuji
    • Journal Title

      Physiological Reports

      Volume: 6 Issue: 14 Pages: e13796-e13796

    • DOI

      10.14814/phy2.13796

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 光誘導性電荷分離分子による脱分極の基盤とその再分極メカニズムの解明2021

    • Author(s)
      Numata T, Sato-Numata K, Imahori H, Murakami T
    • Organizer
      第98回 日本生理学会大会, 名古屋, 日本
    • Related Report
      2020 Annual Research Report
  • [Presentation] Appropriate combinations of herbal components of Japanese Kampo medicines exert laxative actions on colonic epithelium cells through activation of K and Cl channels2020

    • Author(s)
      Numata T, Sato-Numata K, Okada Y, Inoue R
    • Organizer
      第97回 日本生理学会大会, 大分, 日本
    • Related Report
      2020 Annual Research Report
  • [Presentation] 漢方便秘薬の生薬は、適切な組み合わせによって結腸上皮細胞のKおよびClチャネル活性を介して下剤作用を発揮する2020

    • Author(s)
      Tomohiro Numata, Kaori Sato-Numata, Yasunobu Okada, Ryuji Inoue
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 潤腸湯に含まれる生薬成分による分泌性細胞縮小作用の検討2019

    • Author(s)
      沼田 朋大, 佐藤(沼田) かお理, 岡田 泰伸, 井上 隆司
    • Organizer
      第70回西日本生理学会
    • Related Report
      2019 Research-status Report
  • [Presentation] A Turn-on Imaging Probe for GABA(A) Receptors Allows for Construction of Fluorescent Biosensor2019

    • Author(s)
      SAKAMOTO, Seiji; HARADA, Fumio; YAMAURA, Kei; AMAIKE, Kazuma; NUMATA, Tomohiro; INOUE, Ryuji; HAMACHI, Itaru
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Kampo medicine Junchoto promotes intestinal Cl-/water secretion by cAMP-dependent CFTR activation2019

    • Author(s)
      Tomohiro Numata, Kaori Sato-Numata, Yasunobu Okada, Ryuji Inoue
    • Organizer
      The 9th Federation of the Asian and Oceanian Physiological Societies Congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Sensitivity of voltage-dependent Ca2+ channels in rat vasopressin neurons to an anthranilic acid derivative2019

    • Author(s)
      Kaori Sato-Numata, Tomohiro Numata, Yoichi Ueta, Yasunobu Okada
    • Organizer
      The 9th Federation of the Asian and Oceanian Physiological Societies Congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 慢性便秘漢方薬「潤腸湯」の作用機序の解明2018

    • Author(s)
      沼田 朋大、佐藤(沼田) かお理、岡田 泰伸、井上 隆司
    • Organizer
      生体機能と創薬シンポジウム2018
    • Related Report
      2018 Research-status Report
  • [Presentation] 生理数理科学アプローチによるPKD2L1チャネルの新たな電位感受性機構の発見2018

    • Author(s)
      沼田朋大
    • Organizer
      第13回トランスポーター研究会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 光誘発性電荷分離分子を利用した神経興奮制御2018

    • Author(s)
      沼田 朋大
    • Organizer
      第69回西日本生理学会
    • Related Report
      2018 Research-status Report
  • [Presentation] SGLT2 inhibitor ipragliflozin induces breast cancer apoptosis via membrane hyperpolarization and mitochondria dysfunction2018

    • Author(s)
      Shiho Komatsu, Takashi Nomiyama, Tomohiro Numata, Takako Kawanami, Yuriko Hamaguchi, Tomoko Tanaka, Ryuji Inoue, Toshihiko Yanase
    • Organizer
      米国糖尿病学会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] SGLT2阻害薬イプラグリフロジンは乳癌細胞増殖を抑制する2018

    • Author(s)
      小松志保、野見山崇、沼田朋大、堀川剛、川波賢子、濱口百合子、高橋貴理子、岩屋智加予、田中智子、井上隆司、柳瀬敏彦
    • Organizer
      日本糖尿病学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] SGLT2阻害薬イプラグリフロジンは乳癌細胞増殖を抑制する2018

    • Author(s)
      小松志保、野見山崇、沼田朋大、堀川剛、川波賢子、濱口百合子、高橋貴理子、岩屋智加予、田中智子、井上隆司、柳瀬敏彦
    • Organizer
      糖尿病合併症学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Ionic mechanisms of cell volume regulation under hypo/hyperosmotic conditions in AVP neurons and effects of AVP secretion thereon2018

    • Author(s)
      Kaori Sato-Numata, Naomi Yasui, Tomohiro Numata, Yoichi Ueta, Yasunobu Okada
    • Organizer
      神経科学会
    • Related Report
      2018 Research-status Report
  • [Presentation] SGLT2阻害薬イプラグリフロジンは乳癌細胞増殖を抑制する2018

    • Author(s)
      小松志保、野見山崇、沼田朋大、堀川剛、川波賢子、濱口百合子、高橋貴理子、岩屋智加予、田中智子、井上隆司、柳瀬敏彦
    • Organizer
      日本体質医学会
    • Related Report
      2018 Research-status Report
  • [Presentation] SGLT2阻害薬イプラグリフロジンは乳癌細胞増殖を抑制する2018

    • Author(s)
      小松志保、野見山崇、沼田朋大、堀川剛、川波賢子、濱口百合子、高橋貴理子、岩屋智加予、田中智子、井上隆司、柳瀬敏彦
    • Organizer
      内分泌学会
    • Related Report
      2018 Research-status Report
  • [Presentation] SGLT2-I ipragliflozin induces breast cancer apoptosis via membrane hyperpolarization and mitochondria dysfunction2018

    • Author(s)
      S. Komatsu, T. NOMIYAMA, T. Numata, T. Kawanami, Y. Hamaguchi, T. Tanaka, R. Inoue, T. Yanase
    • Organizer
      IDF Diabetes Complications and Foot Congress 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Remarks]

    • URL

      https://resweb2.jhk.adm.fukuoka-u.ac.jp/FukuokaUnivHtml/info/6516/R108J.html

    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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