Updated on 2025/01/05

写真a

 
FUKUSUMI Yoshiyasu
 
Organization
Academic Assembly Institute of Medicine and Dentistry IGAKU KEIRETU Associate Professor
Graduate School of Medical and Dental Sciences Center of Nephrology Associate Professor
Title
Associate Professor
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Degree

  • 博士(医学) ( 2008.3   金沢大学 )

Research Interests

  • 腎臓病態学

Research Areas

  • Life Science / Nephrology

  • Life Science / Cell biology

  • Life Science / Laboratory animal science

  • Life Science / Molecular biology

Research History (researchmap)

  • Niigata University   Graduate School of Medical and Dental Sciences Center of Nephrology   Associate Professor

    2016.4

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  • Niigata University   Graduate School of Medical and Dental Sciences Institute of Nephrology   Associate Professor

    2015.3 - 2016.3

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  • Niigata University   Faculty of Medicine School of Medicine   Assistant Professor

    2011.5 - 2015.2

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  • Niigata University   Graduate School of Medical and Dental Sciences Institute of Nephrology   Assistant Professor

    2011.5 - 2015.2

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  • ドイツヘルムホルツ研究所

    2008.5 - 2011.4

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Research History

  • Niigata University   Faculty of Medicine Institute of Nephrology   Associate Professor

    2016.4

  • Niigata University   Faculty of Medicine Institute of Nephrology   Associate Professor

    2015.3 - 2016.3

  • Niigata University   Faculty of Medicine School of Medicine   Assistant Professor

    2011.5 - 2015.2

  • Niigata University   Faculty of Medicine Institute of Nephrology   Assistant Professor

    2011.5 - 2015.2

Education

  • Kanazawa University   Graduate School, Division of Medical Sciences

    - 2008.3

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    Country: Japan

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Professional Memberships

 

Papers

  • 14-3-3 Proteins stabilize actin and vimentin filaments to maintain processes in renal glomerular podocyte. Reviewed International journal

    Hidenori Yasuda, Yoshiyasu Fukusumi, Ying Zhang, Hiroshi Kawachi

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology   37 ( 10 )   e23168   2023.10

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

    14-3-3 proteins are a ubiquitously expressed family of adaptor proteins. Despite exhibiting high sequence homology, several 14-3-3 isoforms have isoform-specific binding partners and roles. We reported that 14-3-3β interacts with FKBP12 and synaptopodin to maintain the structure of actin fibers in podocytes. However, the precise localization and differential role of 14-3-3 isoforms in kidneys are unclear. Herein, we showed that 14-3-3β in glomeruli was restricted in podocytes, and 14-3-3σ in glomeruli was expressed in podocytes and mesangial cells. Although 14-3-3β was dominantly co-localized with FKBP12 in the foot processes, a part of 14-3-3β was co-localized with Par3 at the slit diaphragm. 14-3-3β interacted with Par3, and FKBP12 bound to 14-3-3β competitively with Par3. Deletion of 14-3-3β enhanced the interaction of Par3 with Par6 in podocytes. Gene silencing for 14-3-3β altered the structure of actin fibers and process formation. 14-3-3β and synaptopodin expression was decreased in podocyte injury models. In contrast, 14-3-3σ in podocytes was expressed in the primary processes. 14-3-3σ interacted with vimentin but not with the actin-associated proteins FKBP12 and synaptopodin. Gene silencing for 14-3-3σ altered the structure of vimentin fibers and process formation. 14-3-3σ and vimentin expression was increased in the early phase of podocyte injury models but was decreased in the late stage. Together, the localization of 14-3-3β at actin cytoskeleton plays a role in maintaining the foot processes and the Par complex in podocytes. In contrast, 14-3-3σ at vimentin cytoskeleton is essential for maintaining primary processes.

    DOI: 10.1096/fj.202300865R

    PubMed

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  • Th17 Cells Participate in Thy1.1 Glomerulonephritis Which Is Ameliorated by Tacrolimus. Reviewed International journal

    Syuhei Watanabe, Ying Zhang, Yoshiyasu Fukusumi, Hidenori Yasuda, Akira Takada, Junichiro J Kazama, Hiroshi Kawachi

    American journal of nephrology   53 ( 5 )   388 - 396   2022

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

    INTRODUCTION: Thy1.1 glomerulonephritis (Thy1.1 GN) in rats is widely used as an experimental model of mesangial proliferative glomerulonephritis (GN). We previously reported that T-helper (Th) cells were accumulated in glomeruli from the early phase of this model and that not Th2 cells but Th1 cells play an important role in the development of glomerular alterations. Although Th17 is reported to be involved in the pathogenesis of several autoimmune diseases, the role of Th17 cells in the pathogenesis of mesangial alterations in Thy1.1 GN remains unclear. METHODS: The kinetics of the infiltration of subsets of Th cells and the expression of IL-17 in Thy1.1 GN were analyzed. Next, the localization and the cell types of IL-17 receptor (IL-17R)-positive cells and IL-6-positive cells were analyzed. Then, the effect of tacrolimus on the expressions of Th17-related cytokines in Thy1.1 GN was analyzed. RESULTS: Not only Th1 cells but also Th17 cells were recruited into glomeruli from the early phase of the disease. mRNA expression of IL-17 in glomeruli was elevated. The increased positive expression of IL-17R was detected in the mesangial area, and some of IL-17R-positive cells were co-stained with IL-6. Tacrolimus treatment ameliorated mesangial alterations by suppressing the expressions of Th17-related cytokines such as IL-17 and IL-6. CONCLUSION: Th17 cells participate in the development of Thy1.1 GN, a mimic of mesangial proliferative GN, and Th17 cells and their related cytokines are pertinent therapeutic targets.

    DOI: 10.1159/000524111

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  • Tacrolimus ameliorates podocyte injury by restoring FK506 binding protein 12 (FKBP12) at actin cytoskeleton. Reviewed International journal

    Hidenori Yasuda, Yoshiyasu Fukusumi, Veniamin Ivanov, Ying Zhang, Hiroshi Kawachi

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology   35 ( 11 )   e21983   2021.11

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

    FKBP12 was identified as a binding protein of tacrolimus (Tac). Tac binds to FKBP12 and exhibits immunosuppressive effects in T cells. Although it is reported that Tac treatment directly ameliorates the dysfunction of the podocyte in nephrotic syndrome, the precise pharmacological mechanism of Tac is not well understood yet. It is also known that FKBP12 functions independently of Tac. However, the localization and the physiological function of FKBP12 are not well elucidated. In this study, we observed that FKBP12 is highly expressed in glomeruli, and the FKBP12 in glomeruli is restricted in podocytes. FKBP12 in cultured podocytes was expressed along the actin cytoskeleton and associated with filamentous actin (F-actin). FKBP12 interacted with the actin-associated proteins 14-3-3 and synaptopodin. RNA silencing for FKBP12 reduced 14-3-3 expression, F-actin staining, and process formation in cultured podocytes. FKBP12 expression was decreased in the nephrotic model caused by adriamycin (ADR) and the cultured podocyte treated with ADR. The process formation was deteriorated in the podocytes treated with ADR. Tac treatment ameliorated these decreases. Tac treatment to the normal cells increased the expression of FKBP12 at F-actin in processes and enhanced process formation. Tac enhanced the interaction of FKBP12 with synaptopodin. These observations suggested that FKBP12 at actin cytoskeleton participates in the maintenance of processes, and Tac treatment ameliorates podocyte injury by restoring FKBP12 at actin cytoskeleton.

    DOI: 10.1096/fj.202101052R

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  • Synbindin Downregulation Participates in Slit Diaphragm Dysfunction. Reviewed International journal

    Veniamin Ivanov, Yoshiyasu Fukusumi, Ying Zhang, Hidenori Yasuda, Meiko Kitazawa, Hiroshi Kawachi

    American journal of nephrology   52 ( 8 )   1 - 10   2021.8

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

    INTRODUCTION: Synbindin, originally identified as a neuronal cytoplasmic molecule, was found in glomeruli. The cDNA subtractive hybridization technique showed the mRNA expression of synbindin in glomeruli was downregulated in puromycin aminonucleoside (PAN) nephropathy, a mimic of minimal-change nephrotic syndrome. METHODS: The expression of synbindin in podocytes was analyzed in normal rats and 2 types of rat nephrotic models, anti-nephrin antibody-induced nephropathy, a pure slit diaphragm injury model, and PAN nephropathy, by immunohistochemical analysis and RT-PCR techniques. To elucidate the function of synbindin, a gene silencing study with human cultured podocytes was performed. RESULTS: Synbindin was mainly expressed at the slit diaphragm area of glomerular epithelial cells (podocytes). In both nephrotic models, decreased mRNA expression and the altered staining of synbindin were already detected at the early phase when proteinuria and the altered staining of nephrin, a key molecule of slit diaphragm, were not detected yet. Synbindin staining was clearly reduced when severe proteinuria was observed. When the cultured podocytes were treated with siRNA for synbindin, the cell changed to a round shape, and filamentous actin structure was clearly altered. The expression of ephrin-B1, a transmembrane protein at slit diaphragm, was clearly lowered, and synaptic vesicle-associated protein 2B (SV2B) was upregulated in the synbindin knockdown cells. CONCLUSION: Synbindin participates in maintaining foot processes and slit diaphragm as a downstream molecule of SV2B-mediated vesicle transport. Synbindin downregulation participates in slit diaphragm dysfunction. Synbindin can be an early marker to detect podocyte injury.

    DOI: 10.1159/000517975

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  • Nephrin-Ephrin-B1-Na+/H+ Exchanger Regulatory Factor 2-Ezrin-Actin Axis Is Critical in Podocyte Injury. Reviewed International journal

    Yoshiyasu Fukusumi, Hidenori Yasuda, Ying Zhang, Hiroshi Kawachi

    The American journal of pathology   191 ( 7 )   1209 - 1226   2021.7

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    Ephrin-B1 is one of the critical components of the slit diaphragm of kidney glomerular podocyte. However, the precise function of ephrin-B1 is unclear. To clarify the function of ephrin-B1, ephrin-B1-associated molecules were studied. RNA-sequencing analysis suggested that Na+/H+ exchanger regulatory factor 2 (NHERF2), a scaffolding protein, is associated with ephrin-B1. NHERF2 was expressed at the apical area and the slit diaphragm, and interacted with the nephrin-ephrin-B1 complex at the slit diaphragm. The nephrin-ephrin-B1-NHERF2 complex interacted with ezrin bound to F-actin. NHERF2 bound ephrin-B1 via its first postsynaptic density protein-95/disks large/zonula occludens-1 domain, and podocalyxin via its second postsynaptic density protein-95/disks large/zonula occludens-1 domain. Both in vitro analyses with human embryonic kidney 293 cells and in vivo study with rat nephrotic model showed that stimulaiton of the slit diaphragm, phosphorylation of nephrin and ephrin-B1, and dephosphorylation of NHERF2 and ezrin, disrupted the linkages of ephrin-B1-NHERF2 and NHERF2-ezrin. It is conceivable that the linkage of nephrin-ephrin-B1-NHERF2-ezrin-actin is a novel critical axis in the podocytes. Ephrin-B1 phosphorylation also disrupted the linkage of an apical transmembrane protein, podocalyxin, with NHERF2-ezrin-actin. The phosphorylation of ephrin-B1 and the consequent dephosphorylation of NHERF2 are critical initiation events leading to podocyte injury.

    DOI: 10.1016/j.ajpath.2021.04.004

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MISC

  • 各種ポドサイト機能分子の病勢診断マーカーとしての有用性の検討:ラットPAN腎症モデルを用いた解析

    金子博司, 若松彩子, 広瀬絵理子, 高島奈津美, 山崎美穂子, 福住好恭, 河内裕

    日本腎臓学会誌   56 ( 3 )   2014

Awards

  • 第36回新潟大学医学研究助成金

    2022.4   新潟大学医学研究助成基金  

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  • 学長賞(若手教員研究奨励)

    2018.11   新潟大学  

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  • 第4回分子腎臓フォーラム優秀賞

    2013.9   分子腎臓フォーラム  

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Research Projects

  • スリット膜機能維持におけるNeurexin-シナプス小胞関連分子相互作用の役割

    Grant number:24K11405

    2024.4 - 2028.3

    System name:科学研究費助成事業

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    福住 好恭, 内許 玉楓, 永井 隆, 河内 裕

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    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

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  • Role of Ephrin-Nephrin-Neurexin complex in maintaining slit diaphragm function

    Grant number:22H03086

    2022.4 - 2025.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

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    Grant amount:\17290000 ( Direct Cost: \13300000 、 Indirect Cost:\3990000 )

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  • 腎糸球体上皮細胞スリット膜におけるNeurexinの役割の解明

    Grant number:20K08587

    2020.4 - 2024.3

    System name:科学研究費助成事業 基盤研究(C)

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    福住 好恭, 張 エイ, 安田 英紀, 河内 裕

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    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    Neurexin1αのスリット膜のバリア構造維持における役割を明らかにするため、本年度(令和3年度)は、(1)Neurexin1α KOマウス糸球体におけるシナプス小胞関連分子群の発現解析、(2)Neurexin1α KOマウス糸球体におけるスリット膜関連分子の局在解析、(3)Neurexin1αとスリット膜関連分子の相互作用解析、(4)マウス培養ポドサイトにおけるNeurexin1αノックダウンの影響について解析した。
    (1)Neurexin1α KOマウス糸球体におけるシナプス小胞関連分子群の発現をリアルタイムPCRにより解析し、KOマウス糸球体でneuroliginやSNARE複合体分子群の発現は変化せず、シナプス小胞分子SV2Bとsynaptotagminの発現が低下することを示した。
    (2)KOマウス糸球体におけるスリット膜関連分子の局在を免疫染色により解析し、KOマウス糸球体でNEPH1とsynaptopodinの局在は変化せず、CD2APとPar-6の局在が変化することを示した。
    (3)Neurexin1αとスリット膜関連分子の相互作用を単離糸球体可溶化材料を用いた免疫沈降法により解析し、NEPH1とsynaptopodinはNeurexin1αと相互作用しないが、CD2APとPar-6は相互作用することを明らかにした。
    (4)マウス培養ポドサイトにNeurexin1α siRNAを処理し、Neurexin1αの発現低下を誘導した。ノックダウンポドサイトで、CD2AP染色の染色性が低下すること、細胞突起が減少することを示した。
    以上より、Neurexin1αはシナプス小胞分子SV2B、synaptotagmin、スリット膜関連分子CD2AP、Par-6の発現、局在に必要であることを示し、Neurexin1αはスリット膜のバリア構造維持に重要であることを明らかにした。

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  • Function of TRPM4 on podocyte

    Grant number:19K08720

    2019.4 - 2023.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

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    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

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  • Novel therapy for nephotic syndrome targetting synapse associated molecules in podocyte

    Grant number:19H03673

    2019.4 - 2022.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    Kawachi Hiroshi

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    Grant amount:\17160000 ( Direct Cost: \13200000 、 Indirect Cost:\3960000 )

    It was demonstrated that synapse associated molecules, SV2B, Neurexin, Ephrin-B1 were expressed in podocyte, and dysfunction of these molecules lead proteinuria. The present study revealed that a unique variant of Neurexin (Neurexin 1a, splice site #4(+)) was expressed in podocyte and interacted with nephrin and CD2AP, critical molecules of slit diaphragm. The interactions played a key role in maintaining the barrier function of slit diaphragm. Ephrin-B, a transmembrane protein was connected to cytoskeletal actin via NHERF2 and Ezrin. The linkage is essential for maintaining barrier function of sit diaphragm. These synapse-associated molecules could be targets for a novel therapy.

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Teaching Experience

  • 生理学実習

    2024
    Institution name:新潟大学