SATO-NUMATA Kaori

写真a

Affiliation

Graduate School of Medicine  Doctorial Course in Medicine  Organ Function-Oriented Medicine  Department of Integrative Physiology
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Research Interests 【 display / non-display 】

  • cell physiology

  • osmotic-sensor

  • cell volume regulation

  • arginine-vasopressin

  • 漢方薬

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Graduating School 【 display / non-display 】

  • 2002.04
    -
    2006.03

    Tokyo Gakugei University     Graduated

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Graduate School 【 display / non-display 】

  • 2006.04
    -
    2011.03

    The Graduate University for Advanced Studies    Doctor's Course  Completed

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Degree 【 display / non-display 】

  • The Graduate University for Advanced Studies -  Doctor (Science)

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Campus Career 【 display / non-display 】

  • 2022.01
    -
    Now

    Akita University   Graduate School of Medicine   Doctorial Course in Medicine   Organ Function-Oriented Medicine   Department of Integrative Physiology   Assistant Professor  

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External Career 【 display / non-display 】

  • 2024.12
    　
    　

    Akita University   Graduate School of Medicine Doctoral Course in Medicine  

  • 2022.01
    -
    2024.11

    Akita University   Graduate School of Medicine Doctoral Course in Medicine   Assistant Professor  

  • 2014.08
    -
    2015.03

    National Institutes of Natural Sciences   Researcher  

  • 2011.04
    -
    2014.07

    National Institutes of Natural Sciences  

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Research Areas 【 display / non-display 】

  • Life Science / Physiology

  • Life Science / Clinical pharmacy

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Research Achievements 【 display / non-display 】

    ◆Original paper【 display / non-display 】

  • Role of Piezo2 in Schwann Cell Volume Regulation and its Impact on Neurotrophic Release Regulation

    Chawapun Suttinont, Katsuyuki Maeno, Mamiko Yano, Kaori Sato-Numata, Tomohiro Numata, Moe Tsutsumi

    Cellular Physiology and Biochemistry   58 ( 4 ) 292 - 310   2024.07  [Refereed]

    Research paper (journal)   Single author

    BACKGROUND/AIMS: Tactile perception relies on mechanoreceptors and nerve fibers, including c-fibers, Aβ-fibers and Aδ-fibers. Schwann cells (SCs) play a crucial role in supporting nerve fibers, with non-myelinating SCs enwrapping c-fibers and myelinating SCs ensheathing Aβ and Aδ fibers. Recent research has unveiled new functions for cutaneous sensory SCs, highlighting the involvement of nociceptive SCs in pain perception and Meissner corpuscle SCs in tactile sensation. Furthermore, Piezo2, previously associated with Merkel cell tactile sensitivity, has been identified in SCs. The goal of this study was to investigate the channels implicated in SC mechanosensitivity and the release process of neurotrophic factor secretion. METHODS: Immortalized IFRS1 SCs and human primary SCs generated two distinct subtypes of SCs: undifferentiated and differentiated SCs. Quantitative PCR was employed to evaluate the expression of differentiation markers and mechanosensitive channels, including TRP channels (TRPV4, TRPM7 and TRPA1) and Piezo channels (Piezo1 and Piezo2). To validate the functionality of specific mechanosensitive channels, Ca2+ imaging and electronic cell sizing experiments were conducted under hypotonic conditions, and inhibitors and siRNAs were used. Protein expression was assessed by Western blotting and immunostaining. Additionally, secretome analysis was performed to evaluate the release of neurotrophic factors in response to hypotonic stimulation, with BDNF, a representative trophic factor, quantified using ELISA. RESULTS: Induction of differentiation increased Piezo2 mRNA expression levels both in IFRS1 and in human primary SCs. Both cell types were responsive to hypotonic solutions, with differentiated SCs displaying a more pronounced response. Gd3+ and FM1-43 effectively inhibited hypotonicity-induced Ca2+ transients in differentiated SCs, implicating Piezo2 channels. Conversely, inhibitors of Piezo1 and TRPM7 (Dooku1 and NS8593, respectively) had no discernible impact. Moreover, Piezo2 in differentiated SCs appeared to participate in regulatory volume decreases (RVD) after cell swelling induced by hypotonic stimulation. A Piezo2 deficiency correlated with reduced RVD and prolonged cell swelling, leading to heightened release of the neurotrophic factor BDNF by upregulating the function of endogenously expressed Ca2+-permeable TRPV4. CONCLUSION: Our study unveils the mechanosensitivity of SCs and implicates Piezo2 channels in the release of neurotrophic factors from SCs. These results suggest that Piezo2 may contribute to RVD, thereby maintaining cellular homeostasis, and may also serve as a negative regulator of neurotrophic factor release. These findings underscore the need for further investigation into the role of Piezo2 in SC function and neurotrophic regulation.

    DOI PubMed

  • Cardioprotective effects of Moku-boi-to and its impact on AngII-induced cardiomyocyte hypertrophy.

    Hideaki Tagashira, Fumiha Abe, Kaori Sato-Numata, Karen Aizawa, Kei Hirasawa, Yoshinobu Kure, Daiki Iwata, Tomohiro Numata

    Frontiers in cell and developmental biology   11   1264076 - 1264076   2023.11  [Refereed]

    Research paper (journal)   Domestic Co-author

    Cardiomyocyte hypertrophy, induced by elevated levels of angiotensin II (AngII), plays a crucial role in cardiovascular diseases. Current therapeutic approaches aim to regress cardiac hypertrophy but have limited efficacy. Widely used Japanese Kampo medicines are highly safe and potential therapeutic agents. This study aims to explore the impact and mechanisms by which Moku-boi-to (MBT), a Japanese Kampo medicine, exerts its potential cardioprotective benefits against AngII-induced cardiomyocyte hypertrophy, bridging the knowledge gap and contributing to the development of novel therapeutic strategies. By evaluating the effects of six Japanese Kampo medicines with known cardiovascular efficiency on AngII-induced cardiomyocyte hypertrophy and cell death, we identified MBT as a promising candidate. MBT exhibited preventive effects against AngII-induced cardiomyocyte hypertrophy, cell death and demonstrated improvements in intracellular Ca2+ signaling regulation, ROS production, and mitochondrial function. Unexpectedly, experiments combining MBT with the AT1 receptor antagonist losartan suggested that MBT may target the AT1 receptor. In an isoproterenol-induced heart failure mouse model, MBT treatment demonstrated significant effects on cardiac function and hypertrophy. These findings highlight the cardioprotective potential of MBT through AT1 receptor-mediated mechanisms, offering valuable insights into its efficacy in alleviating AngII-induced dysfunction in cardiomyocytes. The study suggests that MBT holds promise as a safe and effective prophylactic agent for cardiac hypertrophy, providing a deeper understanding of its mechanisms for cardioprotection against AngII-induced dysfunction.

    DOI PubMed

  • Cell death induction and protection by activation of ubiquitously expressed anion/cation channels. Part 3: the roles and properties of TRPM2 and TRPM7.

    Yasunobu Okada, Tomohiro Numata, Ravshan Z Sabirov, Makiko Kashio, Peter G Merzlyak, Kaori Sato-Numata

    Frontiers in cell and developmental biology   11   1246955 - 1246955   2023.09  [Refereed]

    Research paper (journal)   International Co-author

    Cell volume regulation (CVR) is a prerequisite for animal cells to survive and fulfill their functions. CVR dysfunction is essentially involved in the induction of cell death. In fact, sustained normotonic cell swelling and shrinkage are associated with necrosis and apoptosis, and thus called the necrotic volume increase (NVI) and the apoptotic volume decrease (AVD), respectively. Since a number of ubiquitously expressed ion channels are involved in the CVR processes, these volume-regulatory ion channels are also implicated in the NVI and AVD events. In Part 1 and Part 2 of this series of review articles, we described the roles of swelling-activated anion channels called VSOR or VRAC and acid-activated anion channels called ASOR or PAC in CVR and cell death processes. Here, Part 3 focuses on therein roles of Ca2+-permeable non-selective TRPM2 and TRPM7 cation channels activated by stress. First, we summarize their phenotypic properties and molecular structure. Second, we describe their roles in CVR. Since cell death induction is tightly coupled to dysfunction of CVR, third, we focus on their participation in the induction of or protection against cell death under oxidative, acidotoxic, excitotoxic, and ischemic conditions. In this regard, we pay attention to the sensitivity of TRPM2 and TRPM7 to a variety of stress as well as to their capability to physicall and functionally interact with other volume-related channels and membrane enzymes. Also, we summarize a large number of reports hitherto published in which TRPM2 and TRPM7 channels are shown to be involved in cell death associated with a variety of diseases or disorders, in some cases as double-edged swords. Lastly, we attempt to describe how TRPM2 and TRPM7 are organized in the ionic mechanisms leading to cell death induction and protection.

    DOI PubMed

  • Intermediate conductance Ca2+ -activated potassium channels are activated by functional coupling with stretch-activated nonselective cation channels in cricket myocytes

    Tomohiro Numata, Kaori Sato-Numata, Masami Yoshino

    Frontiers in Insect Science ( Frontiers Media {SA} )  2   2023.01  [Refereed]

    Research paper (journal)   Domestic Co-author

    <jats:p>Cooperative gating of localized ion channels ranges from fine-tuning excitation–contraction coupling in muscle cells to controlling pace-making activity in the heart. Membrane deformation resulting from muscle contraction activates stretch-activated (SA) cation channels. The subsequent Ca<jats:sup>2+</jats:sup> influx activates spatially localized Ca<jats:sup>2+</jats:sup>-sensitive K<jats:sup>+</jats:sup> channels to fine-tune spontaneous muscle contraction. To characterize endogenously expressed intermediate conductance Ca<jats:sup>2+</jats:sup>-activated potassium (IK) channels and assess the functional relevance of the extracellular Ca<jats:sup>2+</jats:sup> source leading to IK channel activity, we performed patch-clamp techniques on cricket oviduct myocytes and recorded single-channel data. In this study, we first investigated the identification of IK channels that could be distinguished from endogenously expressed large-conductance Ca<jats:sup>2+</jats:sup>-activated potassium (BK) channels by adding extracellular Ba<jats:sup>2+</jats:sup>. The single-channel conductance of the IK channel was 62 pS, and its activity increased with increasing intracellular Ca<jats:sup>2+</jats:sup> concentration but was not voltage-dependent. These results indicated that IK channels are endogenously expressed in cricket oviduct myocytes. Second, the Ca<jats:sup>2+</jats:sup> influx pathway that activates the IK channel was investigated. The absence of extracellular Ca<jats:sup>2+</jats:sup> or the presence of Gd<jats:sup>3+</jats:sup> abolished the activity of IK channels. Finally, we investigated the proximity between SA and IK channels. The removal of extracellular Ca<jats:sup>2+</jats:sup>, administration of Ca<jats:sup>2+</jats:sup> to the microscopic region in a pipette, and application of membrane stretching stimulation increased SA channel activity, followed by IK channel activity. Membrane stretch-induced SA and IK channel activity were positively correlated. However, the emergence of IK channel activity and its increase in response to membrane mechanical stretch was not observed without Ca<jats:sup>2+</jats:sup> in the pipette. These results strongly suggest that IK channels are endogenously expressed in cricket oviduct myocytes and that IK channel activity is regulated by neighboring SA channel activity. In conclusion, functional coupling between SA and IK channels may underlie the molecular basis of spontaneous rhythmic contractions.</jats:p>

    DOI PubMed

  • TRPM7 is an essential regulator for volume-sensitive outwardly rectifying anion channel

    Tomohiro Numata, Kaori Sato-Numata, Meredith C. Hermosura, Yasuo Mori, Yasunobu Okada

    Communications Biology ( Springer Science and Business Media LLC )  4 ( 1 ) 599 - 599   2021.12  [Refereed]

    Research paper (journal)   International Co-author

    <title>Abstract</title>Animal cells can regulate their volume after swelling by the regulatory volume decrease (RVD) mechanism. In epithelial cells, RVD is attained through KCl release mediated via volume-sensitive outwardly rectifying Cl<sup>−</sup> channels (VSOR) and Ca<sup>2+</sup>-activated K<sup>+</sup> channels. Swelling-induced activation of TRPM7 cation channels leads to Ca<sup>2+</sup> influx, thereby stimulating the K<sup>+</sup> channels. Here, we examined whether TRPM7 plays any role in VSOR activation. When TRPM7 was knocked down in human HeLa cells or knocked out in chicken DT40 cells, not only TRPM7 activity and RVD efficacy but also VSOR activity were suppressed. Heterologous expression of TRPM7 in TRPM7-deficient DT40 cells rescued both VSOR activity and RVD, accompanied by an increase in the expression of LRRC8A, a core molecule of VSOR. TRPM7 exerts the facilitating action on VSOR activity first by enhancing molecular expression of LRRC8A mRNA through the mediation of steady-state Ca<sup>2+</sup> influx and second by stabilizing the plasmalemmal expression of LRRC8A protein through the interaction between LRRC8A and the <italic>C</italic>-terminal domain of TRPM7. Therefore, TRPM7 functions as an essential regulator of VSOR activity and LRRC8A expression.

    DOI PubMed

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Grant-in-Aid for Scientific Research 【 display / non-display 】

  • Grant-in-Aid for Scientific Research(C)

    Project Year： 2021.04  -  2024.03 

  • Grant-in-Aid for Scientific Research(C)

    Project Year： 2021.04  -  2024.03 

  • Grant-in-Aid for Scientific Research(C)

    Project Year： 2021.04  -  2024.03 

  • Grant-in-Aid for Scientific Research(C)

    Project Year： 2021.04  -  2024.03 

  • Grant-in-Aid for Scientific Research(C)

    Project Year： 2021.04  -  2024.03 

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Presentations 【 display / non-display 】

  • Differences in functional properties between acid-sensitive chloride channels and volume-sensitive chloride channels

    Kaori Sato-Numata  [Invited]

    ICMS (Ion Channel Modulation Symposium) 2024 Japan  (東京大学 弥生講堂 一条ホール)  2024.05  -  2024.05  ソフィオン バイオサイエンス株式会社

  • LRRC8Dのヒト上皮細胞における調節性容積減少への役割

    佐藤（沼田）かお理, 鈴木太郎, 酒井彩子, 森俊太郎, 岡田泰伸, 沼田朋大

    日本生理学会 第100回記念大会  (国立京都国際会館)  2023.03  -  2023.03  日本生理学会第100回記念大会

  • バソプレシンニューロンは高浸透圧刺激に対して分泌性容積減少（SVD）と調節性容積増加（RVI）という相反性容積応答をする

    佐藤（沼田）かお理，沼田朋大，上田陽一，岡田泰伸

    第126回 日本解剖学会総会・全国学術集会, 第98回 日本生理学会大会  2021.03  -  2021.03 

  • Sensitivity of voltage-dependent Ca2+ channels in rat AVP neurons to an anthranilic acid derivative

    Kaori Sato-Numata，Tomohiro Numata，Yoichi Ueta，Yasunobu Okada

    The 9th Federation of Asian and Oceanian Physiological Societies (FAOPS) Congress  2019.03  -  2019.03 

  • Ionic mechanisms of cell volume regulation under hypo/hyperosmotic conditions in AVP neurons and effects of AVP secretion thereon

     [Invited]

    2018.07  -  2018.07 

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