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大学院医学系研究科（医学専攻等） 医学専攻 機能展開医学系 器官・統合生理学講座 |
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2024年12月-継続中
秋田大学 大学院医学系研究科（医学専攻等） 医学専攻 機能展開医学系 器官・統合生理学講座 講師（医学部）
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2022年01月-継続中
秋田大学 大学院医学系研究科（医学専攻等） 医学専攻 機能展開医学系 器官・統合生理学講座 助教
職務経歴（学外） 【 表示 ／ 非表示 】
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2024年12月-継続中
秋田大学 大学院医学系研究科 医学専攻 医学部講師
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2022年01月-2024年11月
秋田大学 大学院医学系研究科 医学専攻 助教
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2021年10月-2021年12月
秋田大学 大学院医学系研究科 日本学術振興会特別研究員
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2018年10月-2021年09月
福岡大学 医学部 日本学術振興会特別研究員
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2015年04月-2018年09月
福岡大学 医学部 日本学術振興会特別研究員
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Moe Tsutsumi, Kaori Sato-Numata, Chawapun Suttinont, Tomohiro Numata
Cureus ( Springer Science and Business Media LLC ) 2025年08月 [査読有り]
研究論文（学術雑誌）
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Boi‐Ogi‐To, a Traditional Japanese Kampo Medicine, Promotes Cellular Excretion of Chloride and Water by Activating Volume‐Sensitive Outwardly Rectifying Anion Channels
Kaori Sato‐Numata, Taro Suzuki, Haruna Saito, Shotaro Kato, Ayako Sakai, Shuntaro Mori, Hajime Nakae, Hitoshi Hasegawa, Yasunobu Okada, Tomohiro Numata
The FASEB Journal ( Wiley ) 39 ( 9 ) 2025年05月 [査読有り]
研究論文（学術雑誌）
ABSTRACT
The Japanese Kampo medicine Boi‐ogi‐to (BOT) is known as an effective therapeutic agent for edema and nephrosis by promoting the excretion of excess body fluids. Despite its empirical effectiveness, scientific evidence supporting its effectiveness remains limited. In this study, we conducted a retrospective study of the effects of BOT administration on the blood test values of patients before and after taking the drug to attempt translational research between basic science and daily clinical practice by focusing on the molecular mechanism of action of BOT in vitro. We found that blood sodium and chloride levels are higher after taking BOT by analyzing the clinical test values before and after taking the drug from 28 patients attending Akita University Hospital. In this light, we measured the cell volume of human embryonic kidney HEK293T cells in vitro in order to investigate the possibility that BOT induces Cl<sup>−</sup> excretion and cell volume reduction. BOT showed concentration‐dependent cell volume reduction with an EC<sub>50</sub> of 686 μg/mL. The volume reduction effect was suppressed by the Cl<sup>−</sup> channel inhibitors DIDS and DCPIB. Furthermore, patch‐clamp studies showed that BOT‐activated Cl<sup>−</sup> currents exhibit outward rectification and time‐dependent inactivation upon depolarization. These biophysical properties of BOT‐induced Cl<sup>−</sup> currents correspond to those of volume‐sensitive outward rectifier (VSOR) anion channels. The Cl<sup>−</sup> currents activated by the administration of BOT were inhibited by applying DIDS, DCPIB, and siRNA targeting the gene of LRRC8A, a core component of the VSOR channel, as well as in LRRC8‐deficient cells. Additionally, BOT‐induced Cl<sup>−</sup> currents were restored by coexpression of LRRC8A/C in LRRC8‐deficient cells. Also, BOT was found to translocate LRRC8A proteins to the plasma membrane. These results demonstrated that BOT activates LRRC8‐containing VSOR channels by delivering LRRC8A to the plasma membrane and induces Cl<sup>−</sup> release, thereby promoting water excretion. -
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年07月 [査読有り]
研究論文（学術雑誌） 単著
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.
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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年11月 [査読有り]
研究論文（学術雑誌） 国内共著
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.
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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年09月 [査読有り]
研究論文（学術雑誌） 国際共著
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.
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ヒスタミン誘発性細胞縮小におけるCl<sup>-</sup>チャネルの関与
青山碧透, 佐藤(沼田)かお理, 酒井彩子, 沼田朋大
日本生理学雑誌(Web) 87 ( 1 ) 2025年
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漢方薬「防已黄耆湯」の水排出機構に関与するCl<sup>-</sup>チャネルの分子同定
鈴木太郎, 齊藤遥菜, 加藤正太郎, 酒井彩子, 佐藤(沼田)かお理, 沼田朋大
日本生理学雑誌(Web) 87 ( 1 ) 2025年
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ヒスタミン誘発性細胞縮小に対する小青竜湯と柴胡桂枝湯の効果
岡田龍馬, 小薮賢太郎, 青山碧透, 菅原弘乃, 酒井彩子, 佐藤(沼田)かお理, 沼田朋大
日本生理学雑誌(Web) 86 ( 1 ) 2024年
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女性研究者支援コンソーシアムあきた賞
2022年12月 女性研究者支援コンソーシアムあきた バソプレシンニューロンの容積調節、及び分泌機構の全容解明
受賞者： 佐藤 かお理 -
入澤宏・彩記念若手研究奨励賞
2017年03月 日本生理学会 LRRC8ファミリーは容積感受性外向整流性アニオンチャネル(VSOR)の活性に関与するが酸感受性外向整流性アニオンチャネル(ASOR)の活性には関与しない
受賞者： 佐藤(沼田) かお理 -
日本生理学会九州奨励賞
2015年10月09日 西日本生理学会 ニューロン酸感受性外向整流性アニオンチャネル（ASOR）のアシドーシス性脳神経細胞障害に対する低温救済への関与
受賞者： 佐藤（沼田）かお理
科研費（文科省・学振）獲得実績 【 表示 ／ 非表示 】
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バソプレシンの分泌調節を担う浸透圧検知性イオンチャネルの同定と機能解析
基盤研究(C)
研究期間: 2021年04月 - 2024年03月 代表者: 沼田 かお理
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バソプレシンの分泌調節を担う浸透圧検知性イオンチャネルの同定と機能解析
基盤研究(C)
研究期間: 2021年04月 - 2024年03月 代表者: 沼田 かお理
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バソプレシンの分泌調節を担う浸透圧検知性イオンチャネルの同定と機能解析
基盤研究(C)
研究期間: 2021年04月 - 2024年03月 代表者: 沼田 かお理
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バソプレシンの分泌調節を担う浸透圧検知性イオンチャネルの同定と機能解析
基盤研究(C)
研究期間: 2021年04月 - 2024年03月 代表者: 沼田 かお理
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バソプレシンの分泌調節を担う浸透圧検知性イオンチャネルの同定と機能解析
基盤研究(C)
研究期間: 2021年04月 - 2024年03月 代表者: 沼田 かお理
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Differences in functional properties between acid-sensitive chloride channels and volume-sensitive chloride channels
Kaori Sato-Numata [招待有り]
ICMS (Ion Channel Modulation Symposium) 2024 Japan (東京大学 弥生講堂 一条ホール) 2024年05月 - 2024年05月 ソフィオン バイオサイエンス株式会社
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パッチクランプ法を用いた2種のアニオンチャネルの薬理学的分別
佐藤(沼田)かお理，沼田朋大 [招待有り]
電気化学会第91回大会 (名古屋大学) 2024年03月 - 2024年03月 電気化学会
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漢方薬「防已黄耆湯」の水排出機構に関与するCl−チャネルの分子同定
鈴木 太郎, 齊藤 遥菜, 加藤 正太郎, 酒井 彩子, 佐藤(沼田) かお理, 沼田 朋大
第56回東北生理談話会 (山形大学) 2024年11月 - 2024年11月 日本生理学会
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セロトニン誘発性細胞縮小に対する半夏瀉心湯の影響
高山 遼, 酒井 彩子, 佐藤(沼田) かお理, 沼田 朋大
第56回東北生理談話会 (山形大学) 2024年11月 - 2024年11月 日本生理学会
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ヒスタミン誘発性細胞縮小におけるCl−チャネルの関与
青山 碧透、佐藤(沼田) かお理、酒井 彩子、沼田 朋大
第56回東北生理談話会 (山形大学) 2024年11月 - 2024年11月 日本生理学会