Updated on 2024/08/14

Information

 

写真a

 
MI XINYA
 
Organization
Faculty of Pharmaceutical Sciences Department of Pharmaceutical Health Care and Sciences Assistant Professor
Title
Assistant Professor
External link

Research Areas

  • Life Science / Physiology

Degree

  • Medical PhD

Research History

  • Kyushu University School of Pharmaceutical Sciences Assistant Professor

    2022.4 - Present

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  • Shiga University of Medical Science Molecular Neuroscience Research Center Specially Appointed Assistant Professor

    2021.10 - 2022.3

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Education

  • Shiga University of Medical Science

    2017.10 - 2022.3

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Research Interests・Research Keywords

  • Research theme：心筋

    Keyword：心筋

    Research period： 2024

  • Research theme：受容体

    Keyword：受容体

    Research period： 2024

  • Research theme：パッチクランプ

    Keyword：パッチクランプ

    Research period： 2024

  • Research theme：イオンチャネル

    Keyword：イオンチャネル

    Research period： 2024

Papers

  • Activation of the urotensin-II receptor by remdesivir induces cardiomyocyte dysfunction Reviewed International journal

    Akiko Ogawa 1,8, Seiya Ohira 1,2,8, Yuri Kato 3, Tatsuya Ikuta 4, Shota Yanagida 5 6, Xinya Mi 3, Yukina Ishii 3, Yasunari Kanda 5, Motohiro Nishida3,7, Asuka Inoue4, Fan-Yan Wei 1

    Communications biology   6 ( 1 )   511   2023.3   （ eISSN:2399-3642 ）

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    Abstract

    Remdesivir is an antiviral drug used for COVID-19 treatment worldwide. Cardiovascular side effects have been associated with remdesivir; however, the underlying molecular mechanism remains unknown. Here, we performed a large-scale G-protein-coupled receptor screening in combination with structural modeling and found that remdesivir is a selective, partial agonist for urotensin-II receptor (UTS2R) through the Gα<sub>i/o</sub>-dependent AKT/ERK axis. Functionally, remdesivir treatment induced prolonged field potential and APD<sub>90</sub> in human induced pluripotent stem cell (iPS)-derived cardiomyocytes and impaired contractility in both neonatal and adult cardiomyocytes, all of which mirror the clinical pathology. Importantly, remdesivir-mediated cardiac malfunctions were effectively attenuated by antagonizing UTS2R signaling. Finally, we characterized the effect of 110 single-nucleotide variants in UTS2R gene reported in genome database and found four missense variants that show gain-of-function effects in the receptor sensitivity to remdesivir. Collectively, our study illuminates a previously unknown mechanism underlying remdesivir-related cardiovascular events and that genetic variations of UTS2R gene can be a potential risk factor for cardiovascular events during remdesivir treatment, which collectively paves the way for a therapeutic opportunity to prevent such events in the future.

    DOI： 10.1038/s42003-023-04888-x

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    Other Link： https://www.nature.com/articles/s42003-023-04888-x

  • Knockout of Purinergic P2Y6 Receptor Fails to Improve Liver Injury and Inflammation in Non-Alcoholic Steatohepatitis Reviewed International journal

    Kazuhiro Nishiyama 1, Kohei Ariyoshi 1, Akiyuki Nishimura 2 3, Yuri Kato 1, Xinya Mi 1, Hitoshi Kurose 1, Sang Geon Kim 4, Motohiro Nishida 1 2 3

    International Journal of Molecular Sciences   24 ( 4 )   2023.2   （ ISSN:16616596 eISSN:1422-0067 ）

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    Language：English   Publishing type：Research paper (scientific journal)  

    Nonalcoholic steatohepatitis (NASH) is a disease that progresses from nonalcoholic fatty liver (NAFL) and which is characterized by inflammation and fibrosis. The purinergic P2Y6 receptor (P2Y6R) is a pro-inflammatory Gq/G12 family protein-coupled receptor and reportedly contributes to intestinal inflammation and cardiovascular fibrosis, but its role in liver pathogenesis is unknown. Human genomics data analysis revealed that the liver P2Y6R mRNA expression level is increased during the progression from NAFL to NASH, which positively correlates with inductions of C-C motif chemokine 2 (CCL2) and collagen type I α1 chain (Col1a1) mRNAs. Therefore, we examined the impact of P2Y6R functional deficiency in mice crossed with a NASH model using a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Feeding CDAHFD for 6 weeks markedly increased P2Y6R expression level in mouse liver, which was positively correlated with CCL2 mRNA induction. Unexpectedly, the CDAHFD treatment for 6 weeks increased liver weights with severe steatosis in both wild-type (WT) and P2Y6R knockout (KO) mice, while the disease marker levels such as serum AST and liver CCL2 mRNA in CDAHFD-treated P2Y6R KO mice were rather aggravated compared with those of CDAHFD-treated WT mice. Thus, P2Y6R may not contribute to the progression of liver injury, despite increased expression in NASH liver.

    DOI： 10.3390/ijms24043800

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  • 肺高血圧症治療の新戦略 TRPC3/6タンパク質のアイソフォーム特異的な役割を標的とする創薬 Reviewed

    西田 基宏 , 西山 和宏 加藤 百合 , Mi Xinya , 西村 明幸

    日本心脈管作動物質学会   2023.1

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    Language：Japanese   Publishing type：Research paper (scientific journal)  

    DOI： SN : 0911-4637医中誌Web ID : X522520015

  • Propofol, an Anesthetic Agent, Inhibits HCN Channels through the Allosteric Modulation of the cAMP-Dependent Gating Mechanism. Reviewed International journal

    Morihiro Shimizu, Xinya Mi, Futoshi Toyoda, Akiko Kojima, Wei-Guang Ding, Yutaka Fukushima, Mariko Omatsu-Kanbe, Hirotoshi Kitagawa, Hiroshi Matsuura

    Biomolecules   12 ( 4 )   2022.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    Propofol is a broadly used intravenous anesthetic agent that can cause cardiovascular effects, including bradycardia and asystole. A possible mechanism for these effects is slowing cardiac pacemaker activity due to inhibition of the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels. However, it remains unclear how propofol affects the allosteric nature of the voltage- and cAMP-dependent gating mechanism in HCN channels. To address this aim, we investigated the effect of propofol on HCN channels (HCN4 and HCN2) in heterologous expression systems using a whole-cell patch clamp technique. The extracellular application of propofol substantially suppressed the maximum current at clinical concentrations. This was accompanied by a hyperpolarizing shift in the voltage dependence of channel opening. These effects were significantly attenuated by intracellular loading of cAMP, even after considering the current modification by cAMP in opposite directions. The differential degree of propofol effects in the presence and absence of cAMP was rationalized by an allosteric gating model for HCN channels, where we assumed that propofol affects allosteric couplings between the pore, voltage-sensor, and cyclic nucleotide-binding domain (CNBD). The model predicted that propofol enhanced autoinhibition of pore opening by unliganded CNBD, which was relieved by the activation of CNBD by cAMP. Taken together, these findings reveal that propofol acts as an allosteric modulator of cAMP-dependent gating in HCN channels, which may help us to better understand the clinical action of this anesthetic drug.

    DOI： 10.3390/biom12040570

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  • Atypically Shaped Cardiomyocytes (ACMs): The Identification, Characterization and New Insights into a Subpopulation of Cardiomyocytes Reviewed International journal

    Mariko Omatsu-Kanbe 1, Ryo Fukunaga 1, Xinya Mi 1, Hiroshi Matsuura 1

    Biomolecules   12 ( 7 )   896 - 896   2022.1   （ eISSN:2218-273X ）

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

    In the adult mammalian heart, no data have yet shown the existence of cardiomyocyte-differentiable stem cells that can be used to practically repair the injured myocardium. Atypically shaped cardiomyocytes (ACMs) are found in cultures of the cardiomyocyte-removed fraction obtained from cardiac ventricles from neonatal to aged mice. ACMs are thought to be a subpopulation of cardiomyocytes or immature cardiomyocytes, most closely resembling cardiomyocytes due to their spontaneous beating, well-organized sarcomere and the expression of cardiac-specific proteins, including some fetal cardiac gene proteins. In this review, we focus on the characteristics of ACMs compared with ventricular myocytes and discuss whether these cells can be substitutes for damaged cardiomyocytes. ACMs reside in the interstitial spaces among ventricular myocytes and survive under severely hypoxic conditions fatal to ventricular myocytes. ACMs have not been observed to divide or proliferate, similar to cardiomyocytes, but they maintain their ability to fuse with each other. Thus, it is worthwhile to understand the role of ACMs and especially how these cells perform cell fusion or function independently in vivo. It may aid in the development of new approaches to cell therapy to protect the injured heart or the clarification of the pathogenesis underlying arrhythmia in the injured heart.

    DOI： 10.3390/biom12070896

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  • Selective activation of adrenoceptors potentiates IKs current in pulmonary vein cardiomyocytes through the protein kinase A and C signaling pathways. Reviewed International journal

    Xinya Mi, Wei-Guang Ding, Futoshi Toyoda, Akiko Kojima, Mariko Omatsu-Kanbe, Hiroshi Matsuura

    Journal of molecular and cellular cardiology   161   86 - 97   2021.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.yjmcc.2021.08.004

  • Characterization and functional role of rapid- and slow-activating delayed rectifier K+ currents in atrioventricular node cells of guinea pigs. Reviewed International journal

    Mayumi Yuasa, Akiko Kojima, Xinya Mi, Wei-Guang Ding, Mariko Omatsu-Kanbe, Hirotoshi Kitagawa, Hiroshi Matsuura

    Pflugers Archiv : European journal of physiology   473 ( 12 )   1885 - 1898   2021.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1007/s00424-021-02617-z

  • Elevation of propofol sensitivity of cardiac IKs channel by KCNE1 polymorphism D85N. Reviewed International journal

    Akiko Kojima, Xinya Mi, Yutaka Fukushima, Wei-Guang Ding, Mariko Omatsu-Kanbe, Hiroshi Matsuura

    British journal of pharmacology   178 ( 13 )   2690 - 2708   2021.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1111/bph.15460

  • An Antegrade Perfusion Method for Cardiomyocyte Isolation from Mice. Reviewed International journal

    Mariko Omatsu-Kanbe, Ryo Fukunaga, Xinya Mi, Hiroshi Matsuura

    Journal of visualized experiments : JoVE   ( 171 )   2021.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.3791/61866

  • Positive Inotropic Effects of ATP Released via the Maxi-Anion Channel in Langendorff-Perfused Mouse Hearts Subjected to Ischemia-Reperfusion Reviewed International journal

    Hiroshi Matsuura 1, Akiko Kojima 2, Yutaka Fukushima 2, Yu Xie 1, Xinya Mi 1, Ravshan Z Sabirov 3, Yasunobu Okada 4 5 6

    Front Cell Dev Biol   2021.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.3389/fcell.2021.597997

  • Open-channel blocking action of volatile anaesthetics desflurane and sevoflurane on human voltage-gated Kv 1.5 channel. Reviewed International journal

    Yutaka Fukushima, Akiko Kojima, Xinya Mi, Wei-Guang Ding, Hirotoshi Kitagawa, Hiroshi Matsuura

    British journal of pharmacology   177 ( 16 )   3811 - 3827   2020.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1111/bph.15105

  • Supersulfide catabolism participates in maladaptive remodeling of cardiac cells

    Zhou, LCZ; Nishimura, A; Umezawa, K; Kato, Y; Mi, XY; Ito, T; Urano, Y; Akaike, T; Nishida, M

    JOURNAL OF PHARMACOLOGICAL SCIENCES   155 ( 4 )   121 - 130   2024.8   （ ISSN:1347-8613 eISSN:1347-8648 ）

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    Language：English   Publisher：Journal of Pharmacological Sciences  

    The atrophic myocardium resulting from mechanical unloading and nutritional deprivation is considered crucial as maladaptive remodeling directly associated with heart failure, as well as interstitial fibrosis. Conversely, myocardial hypertrophy resulting from hemodynamic loading is perceived as compensatory stress adaptation. We previously reported the abundant presence of highly redox-active polysulfide molecules, termed supersulfide, with two or more sulfur atoms catenated in normal hearts, and the supersulfide catabolism in pathologic hearts after myocardial infarction correlated with worsened prognosis of heart failure. However, the impact of supersulfide on myocardial remodeling remains unclear. Here, we investigated the involvement of supersulfide metabolism in cardiomyocyte remodeling, using a model of adenosine 5′-triphosphate (ATP) receptor-stimulated atrophy and endothelin-1 receptor-stimulated hypertrophy in neonatal rat cardiomyocytes. Results revealed contrasting changes in intracellular supersulfide and its catabolite, hydrogen sulfide (H2S), between cardiomyocyte atrophy and hypertrophy. Stimulation of cardiomyocytes with ATP decreased supersulfide activity, while H2S accumulation itself did not affect cardiomyocyte atrophy. This supersulfide catabolism was also involved in myofibroblast formation of neonatal rat cardiac fibroblasts. Thus, unraveling supersulfide metabolism during myocardial remodeling may lead to the development of novel therapeutic strategies to improve heart failure.

    DOI： 10.1016/j.jphs.2024.05.002

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  • Inhibition of dynamin-related protein 1-filamin interaction improves systemic glucose metabolism

    Kato, Y; Ariyoshi, K; Nohara, Y; Matsunaga, N; Shimauchi, T; Shindo, N; Nishimura, A; Mi, XY; Kim, SG; Ide, T; Kawanishi, E; Ojida, A; Nakashima, N; Mori, Y; Nishida, M

    BRITISH JOURNAL OF PHARMACOLOGY   2024.7   （ ISSN:0007-1188 eISSN:1476-5381 ）

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    Language：English   Publisher：British Journal of Pharmacology  

    Background and purpose: Maintaining mitochondrial quality is attracting attention as a new strategy to treat diabetes and diabetic complications. We previously reported that mitochondrial hyperfission by forming a protein complex between dynamin-related protein (Drp) 1 and filamin, mediates chronic heart failure and cilnidipine, initially developed as an L/N-type Ca2+ channel blocker, improves heart failure by inhibiting Drp1-filamin protein complex. We investigated whether cilnidipine improves hyperglycaemia of various diabetic mice models. Experimental Approach: Retrospective analysis focusing on haemoglobin A1c (HbA1c) was performed in hypertensive and hyperglycaemic patients taking cilnidipine and amlodipine. After developing diabetic mice by streptozotocin (STZ) treatment, an osmotic pump including drug was implanted intraperitoneally, followed by weekly measurements of blood glucose levels. Mitochondrial morphology was analysed by electron microscopy. A Ca2+ channel-insensitive cilnidipine derivative (1,4-dihydropyridine [DHP]) was synthesized and its pharmacological effect was evaluated using obese (ob/ob) mice fed with high-fat diet (HFD). Key Results: In patients, cilnidipine was superior to amlodipine in HbA1c lowering effect. Cilnidipine treatment improved systemic hyperglycaemia and mitochondrial morphological abnormalities in STZ-exposed mice, without lowering blood pressure. Cilnidipine failed to improve hyperglycaemia of ob/ob mice, with suppressing insulin secretion. 1,4-DHP improved hyperglycaemia and mitochondria abnormality in ob/ob mice fed HFD. 1,4-DHP and cilnidipine improved basal oxygen consumption rate of HepG2 cells cultured under 25 mM glucose. Conclusion and implications: Inhibition of Drp1-filamin protein complex formation becomes a new strategy for type 2 diabetes treatment.

    DOI： 10.1111/bph.16487

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  • Inhibition of Drp1-Filamin Protein Complex Prevents Hepatic Lipid Droplet Accumulation by Increasing Mitochondria-Lipid Droplet Contact. International journal

    Kohei Ariyoshi, Kazuhiro Nishiyama, Yuri Kato, Xinya Mi, Tomoya Ito, Yasu-Taka Azuma, Akiyuki Nishimura, Motohiro Nishida

    International journal of molecular sciences   25 ( 10 )   2024.5   （ ISSN:1661-6596 eISSN:1422-0067 ）

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    Lipid droplet (LD) accumulation in hepatocytes is one of the major symptoms associated with fatty liver disease. Mitochondria play a key role in catabolizing fatty acids for energy production through β-oxidation. The interplay between mitochondria and LD assumes a crucial role in lipid metabolism, while it is obscure how mitochondrial morphology affects systemic lipid metabolism in the liver. We previously reported that cilnidipine, an already existing anti-hypertensive drug, can prevent pathological mitochondrial fission by inhibiting protein-protein interaction between dynamin-related protein 1 (Drp1) and filamin, an actin-binding protein. Here, we found that cilnidipine and its new dihydropyridine (DHP) derivative, 1,4-DHP, which lacks Ca2+ channel-blocking action of cilnidipine, prevent the palmitic acid-induced Drp1-filamin interaction, LD accumulation and cytotoxicity of human hepatic HepG2 cells. Cilnidipine and 1,4-DHP also suppressed the LD accumulation accompanied by reducing mitochondrial contact with LD in obese model and high-fat diet-fed mouse livers. These results propose that targeting the Drp1-filamin interaction become a new strategy for the prevention or treatment of fatty liver disease.

    DOI： 10.3390/ijms25105446

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  • Cardiac remodeling: novel pathophysiological mechanisms and therapeutic strategies

    Nishida, M; Mi, XY; Ishii, Y; Kato, Y; Nishimura, A

    JOURNAL OF BIOCHEMISTRY   2024.3   （ ISSN:0021-924X eISSN:1756-2651 ）

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  • Supersulfide prevents cigarette smoke extract-induced mitochondria hyperfission and cardiomyocyte early senescence by inhibiting Drp1-filamin complex formation Invited Reviewed International journal

    Akiyuki Nishimura 1, Liuchenzi Zhou 2, Yuri Kato 3, Xinya Mi 3, Tomoya Ito 2, Yuko Ibuki 4, Yasunari Kanda 5, Motohiro Nishida 6

    2024.2

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  • Pharmacological Activation of TRPC6 Channel Prevents Colitis Progression Reviewed International journal

    Kazuhiro Nishiyama 1 2, Yuri Kato 1, Akiyuki Nishimura 3 4 5, Xinya Mi 1, Ryu Nagata 6, Yasuo Mori 7, Yasu-Taka Azuma 2, Motohiro Nishida 1 3 4 5 8

    2024.2

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： DOI: 10.3390/ijms25042401

  • Supersulfide prevents cigarette smoke extract-induced mitochondria hyperfission and cardiomyocyte early senescence by inhibiting Drp1-filamin complex formation(タイトル和訳中)

    Nishimura Akiyuki, Zhou Liuchenzi, Kato Yuri, Mi Xinya, Ito Tomoya, Ibuki Yuko, Kanda Yasunari, Nishida Motohiro

    Journal of Pharmacological Sciences   154 ( 2 )   127 - 135   2024.2   （ ISSN:1347-8613 ）

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    Language：English   Publisher：(公社)日本薬理学会  

  • Supersulfide prevents cigarette smoke extract-induced mitochondria hyperfission and cardiomyocyte early senescence by inhibiting Drp1-filamin complex formation Reviewed

    Akiyuki Nishimura, Liuchenzi Zhou, Yuri Kato, Xinya Mi, Tomoya Ito, Yuko Ibuki, Yasunari Kanda, Motohiro Nishida

    Journal of Pharmacological Sciences   154 ( 2 )   127 - 135   2024.2   （ ISSN:1347-8613 eISSN:1347-8648 ）

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.jphs.2023.12.008

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  • Pharmacological Activation of TRPC6 Channel Prevents Colitis Progression. Reviewed International journal

    Kazuhiro Nishiyama, Yuri Kato, Akiyuki Nishimura, Xinya Mi, Ryu Nagata, Yasuo Mori, Yasu-Taka Azuma, Motohiro Nishida

    International journal of molecular sciences   25 ( 4 )   2024.2   （ ISSN:1661-6596 eISSN:1422-0067 ）

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    We recently reported that transient receptor potential canonical (TRPC) 6 channel activity contributes to intracellular Zn2+ homeostasis in the heart. Zn2+ has also been implicated in the regulation of intestinal redox and microbial homeostasis. This study aims to investigate the role of TRPC6-mediated Zn2+ influx in the stress resistance of the intestine. The expression profile of TRPC1-C7 mRNAs in the actively inflamed mucosa from inflammatory bowel disease (IBD) patients was analyzed using the GEO database. Systemic TRPC3 knockout (KO) and TRPC6 KO mice were treated with dextran sulfate sodium (DSS) to induce colitis. The Zn2+ concentration and the mRNA expression levels of oxidative/inflammatory markers in colon tissues were quantitatively analyzed, and gut microbiota profiles were compared. TRPC6 mRNA expression level was increased in IBD patients and DSS-treated mouse colon tissues. DSS-treated TRPC6 KO mice, but not TRPC3 KO mice, showed severe weight loss and increased disease activity index compared with DSS-treated WT mice. The mRNA abundances of antioxidant proteins were basically increased in the TRPC6 KO colon, with changes in gut microbiota profiles. Treatment with TRPC6 activator prevented the DSS-induced colitis progression accompanied by increasing Zn2+ concentration. We suggest that TRPC6-mediated Zn2+ influx activity plays a key role in stress resistance against IBD, providing a new strategy for treating colitis.

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  • 肺高血圧症治療の新戦略 TRPC3/6タンパク質のアイソフォーム特異的な役割を標的とする創薬 Reviewed

    西田 基宏, 西山 和宏, 加藤 百合, Mi Xinya, 西村 明幸

    血管   46 ( 1 )   38 - 38   2023.1   （ ISSN:0911-4637 ）

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    Language：Japanese   Publisher：日本心脈管作動物質学会  

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Professional Memberships

  • 日本生理学学会

    2021.12 - 2022.12

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  • 日本生理学学会