KIKUCHI Shin

写真a

Affiliation

School of Medicine, Department of Anatomy (1)

Job title

Associate Professor
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Education 【 display / non-display 】

  • 　
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    2006

    Sapporo Medical University   博士後期課程   保健医療学研究科  

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    2001

    Sapporo Medical University   School of Health Sciences   Department of Physical Therapy  

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Degree 【 display / non-display 】

  • 札幌医科大学   PhD(physical therapy)

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Research Experience 【 display / non-display 】

  • 2022.10
    -
    Now

    Sapporo Medical University   School of Medicine   Associate professor

  • 2016.06
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    2022.09

    Sapporo Medical University   School of Medicine   Instructor

  • 2007.04
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    2016.05

    Sapporo Medical University School of Medicine   医学部   助教

    助教

  • 2005.04
    -
    2007.03

    Sapporo Medical Univesity   School of Medicine   Instructo

    Instructo

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Professional Memberships 【 display / non-display 】

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    THE JAPANESE ASSOCIATION OF ANATOMISTS

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    THE JAPAN NEUROSCIENCE SOCIETY

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    Society for Neuroscience

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    JAPANESE ASSOCIATION OF PHYSICAL THERAPY FUNDAMENTALS

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    JAPANESE PHYSICAL THERAPY ASSOCIATION

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Research Areas 【 display / non-display 】

  • Life sciences   Rehabilitation science  

  • Life sciences   Anatomy  

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Affiliation 【 display / non-display 】

  • Sapporo Medical University   School of Medicine, 1st Dept.of Anatomy   Associate Professor  

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Research Interests 【 display / non-display 】

  • ASIC2

  • neuroanatomy

  • histology

  • 有毛細胞

  • イオンチャンネル

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Papers 【 display / non-display 】

  • Oxygen-Glucose Deprivation Decreases the Motility and Length of Axonal Mitochondria in Cultured Dorsal Root Ganglion Cells of Rats.

    Shin Kikuchi, Takayuki Kohno, Takashi Kojima, Haruyuki Tatsumi, Yuki Ohsaki, Takafumi Ninomiya

    Cellular and molecular neurobiology    2022.06  [International journal]

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    Controlling axonal mitochondria is important for maintaining normal function of the neural network. Oxygen-glucose deprivation (OGD), a model used for mimicking ischemia, eventually induces neuronal cell death similar to axonal degeneration. Axonal mitochondria are disrupted during OGD-induced neural degeneration; however, the mechanism underlying mitochondrial dysfunction has not been completely understood. We focused on the dynamics of mitochondria in axons exposed to OGD; we observed that the number of motile mitochondria significantly reduced in 1 h following OGD exposure. In our observation, the decreased length of stationary mitochondria was affected by the following factors: first, the halt of motile mitochondria; second, the fission of longer stationary mitochondria; and third, a transformation from tubular to spherical shape in OGD-exposed axons. Motile mitochondria reduction preceded stationary mitochondria fragmentation in OGD exposure; these conditions induced the decrease of stationary mitochondria in three different ways. Our results suggest that mitochondrial morphological changes precede the axonal degeneration while ischemia-induced neurodegeneration.

    DOI PubMed

  • Inhibition of HDAC and Signal Transduction Pathways Induces Tight Junctions and Promotes Differentiation in p63-Positive Salivary Duct Adenocarcinoma.

    Masaya Nakano, Kizuku Ohwada, Yuma Shindo, Takumi Konno, Takayuki Kohno, Shin Kikuchi, Mitsuhiro Tsujiwaki, Daichi Ishii, Soshi Nishida, Takuya Kakuki, Kazufumi Obata, Ryo Miyata, Makoto Kurose, Atsushi Kondoh, Kenichi Takano, Takashi Kojima

    Cancers   14 ( 11 )  2022.05  [International journal]

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    BACKGROUND: The p53 family p63 is essential for the proliferation and differentiation of various epithelial basal cells. It is overexpressed in several cancers, including salivary gland neoplasia. Histone deacetylases (HDACs) are thought to play a crucial role in carcinogenesis, and HDAC inhibitors downregulate p63 expression in cancers. METHODS: In the present study, to investigate the roles and regulation of p63 in salivary duct adenocarcinoma (SDC), human SDC cell line A253 was transfected with siRNA-p63 or treated with the HDAC inhibitors trichostatin A (TSA) and quisinostat (JNJ-26481585). RESULTS: In a DNA array, the knockdown of p63 markedly induced mRNAs of the tight junction (TJ) proteins cingulin (CGN) and zonula occuludin-3 (ZO-3). The knockdown of p63 resulted in the recruitment of the TJ proteins, the angulin-1/lipolysis-stimulated lipoprotein receptor (LSR), occludin (OCLN), CGN, and ZO-3 at the membranes, preventing cell proliferation, and leading to increased cell metabolism. Treatment with HDAC inhibitors downregulated the expression of p63, induced TJ structures, recruited the TJ proteins, increased the epithelial barrier function, and prevented cell proliferation and migration. CONCLUSIONS: p63 is not only a diagnostic marker of salivary gland neoplasia, but it also promotes the malignancy. Inhibition of HDAC and signal transduction pathways is, therefore, useful in therapy for p63-positive SDC cells.

    DOI PubMed

  • FOXO3/TGF-β signal-dependent ciliogenesis and cell functions during differentiation of temperature-sensitive mouse cochlear precursor hair cells.

    Takuya Kakuki, Takayuki Kohno, Soshi Nishida, Takumi Konno, Shin Kikuchi, Kizuku Ohwada, Masaya Nakano, Mitsuki Tezuka, Kenichi Takano, Takashi Kojima

    Histochemistry and cell biology   157 ( 4 ) 415 - 426  2022.04  [International journal]

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    The transcription factor FOXO3 is necessary to preserve cochlear hair cells. Growth factors, including TGF-β, closely contribute to cochlear hair cell regeneration. In the present study, to investigate the roles of FOXO3 in the ciliogenesis and cell functions of cochlear hair cells, UB/OC-2 temperature-sensitive mouse cochlear precursor hair cells were treated with TGF-β receptor type 1 inhibitor EW-7197 or EGF receptor inhibitor AG-1478 after transfection with or without siRNA-FOXO3a. GeneChip analysis revealed that treatment with EW-7197 increased Foxo3 genes and decreased genes of Smads. During cell differentiation, treatment with EW-7197 or AG-1478 induced an increase in length of cilia-like structures that were positive for acetylated tubulin and inhibited cell migration. Treatment with EW-7197 also increased cell metabolism measured as mitochondrial basal respiration (oxygen consumption rate). The effects of EW-7197 were stronger than those of AG-1478. Knockdown of FOXO3 prevented the growth of cilia-like structures induced by EW-7197 or AG-1478 and induced cell migration under treatment with EW-7197. No change of the epithelial cell polarity molecule PAR3 was observed with any treatment. Treatment with the antimicrobial agent amikacin prevented the growth of cilia-like structures induced by EW-7197 and induced apoptosis. Pretreatment with the glucocorticoid dexamethasone inhibited the apoptosis induced by amikacin. This in vitro model of mouse cochlear hair cells suggests that FOXO3/TGF-β signaling plays a crucial role in ciliogenesis and cell functions during differentiation of cochlear hair cells. This model is useful for analysis of the mechanisms of hearing loss and to find therapeutic agents to prevent it.

    DOI PubMed

  • The Roles of Tricellular Tight Junction Protein Angulin-1/Lipolysis-Stimulated Lipoprotein Receptor (LSR) in Endometriosis and Endometrioid-Endometrial Carcinoma.

    Hiroshi Shimada, Takayuki Kohno, Takumi Konno, Tadahi Okada, Kimihito Saito, Yuma Shindo, Shin Kikuchi, Mitsuhiro Tsujiwaki, Marie Ogawa, Motoki Matsuura, Tsuyoshi Saito, Takashi Kojima

    Cancers   13 ( 24 )  2021.12  [International journal]

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    Tight junction proteins play roles beyond permeability barriers functions and control cell proliferation and differentiation. The relation between tight junctions and the signal transduction pathways affects cell growth, invasion and migration. Abnormality of tight junction proteins closely contributes to epithelial mesenchymal transition (EMT) and malignancy of various cancers. Angulin-1/lipolysis-stimulated lipoprotein receptor (LSR) forms tricellular contacts that has a barrier function. Downregulation of angulin-1/LSR correlates with the malignancy in various cancers, including endometrioid-endometrial carcinoma (EEC). These alterations have been shown to link to not only multiple signaling pathways such as Hippo/YAP, HDAC, AMPK, but also cell metabolism in ECC cell line Sawano. Moreover, loss of angulin-1/LSR upregulates claudin-1, and loss of apoptosis stimulating p53 protein 2 (ASPP2) downregulates angulin-1/LSR. Angulin-1/LSR and ASPP2 concentrate at both midbody and centrosome in cytokinesis. In EEC tissues, angulin-1/LSR and ASPP2 are reduced and claudin-2 is overexpressed during malignancy, while in the tissues of endometriosis changes in localization of angulin-1/LSR and claudin-2 are seen. This review highlights how downregulation of angulin-1/LSR promotes development of endometriosis and EEC and discusses about the roles of angulin-1/LSR and its related proteins, including claudins and ASPP2.

    DOI PubMed

  • The Role of Galanin in Cerebellar Granule Cell Migration in the Early Postnatal Mouse during Normal Development and after Injury.

    Yutaro Komuro, Ludovic Galas, Yury M Morozov, Jennifer K Fahrion, Emilie Raoult, Alexis Lebon, Amanda K Tilot, Shin Kikuchi, Nobuhiko Ohno, David Vaudry, Pasko Rakic, Hitoshi Komuro

    The Journal of neuroscience : the official journal of the Society for Neuroscience   41 ( 42 ) 8725 - 8741  2021.10  [International journal]

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    Galanin, one of the most inducible neuropeptides, is widely present in developing brains, and its expression is altered by pathologic events (e.g., epilepsy, ischemia, and axotomy). The roles of galanin in brain development under both normal and pathologic conditions have been hypothesized, but the question of how galanin is involved in fetal and early postnatal brain development remains largely unanswered. In this study, using granule cell migration in the cerebellum of early postnatal mice (both sexes) as a model system, we examined the role of galanin in neuronal cell migration during normal development and after brain injury. Here we show that, during normal development, endogenous galanin participates in accelerating granule cell migration via altering the Ca2+ and cAMP signaling pathways. Upon brain injury induced by the application of cold insults, galanin levels decrease at the lesion sites, but increase in the surroundings of lesion sites. Granule cells exhibit the following corresponding changes in migration: (1) slowing down migration at the lesion sites; and (2) accelerating migration in the surroundings of lesion sites. Experimental manipulations of galanin signaling reduce the lesion site-specific changes in granule cell migration, indicating that galanin plays a role in such deficits in neuronal cell migration. The present study suggests that manipulating galanin signaling may be a potential therapeutic target for acutely injured brains during development.SIGNIFICANCE STATEMENT Deficits in neuronal cell migration caused by brain injury result in abnormal development of cortical layers, but the underlying mechanisms remain to be determined. Here, we report that on brain injury, endogenous levels of galanin, a neuropeptide, are altered in a lesion site-specific manner, decreasing at the lesion sites but increasing in the surroundings of lesion sites. The changes in galanin levels positively correlate with the migration rate of immature neurons. Manipulations of galanin signaling ameliorate the effects of injury on neuronal migration and cortical layer development. These results shed a light on galanin as a potential therapeutic target for acutely injured brains during development.

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Misc 【 display / non-display 】

  • 65th Annual Congress of the Japan Society of Acupuncture and Moxibustion in Hokkaido : Acupuncture playing a significant role in Japanese medicine : acupuncture remedy and medical cooperation : Acupuncture as an "Info-Med" : Aiming at prevention from cognitive disorders in regional medicine : a proposal of "Full-Powered Medicine"

    辰巳 治之, 溝口 照悟, 新見 隆彦, 太田 秀造, 竹中 郁夫, 菊池 真, 市川 量一, 二宮 孝文, 戸倉 一, 山口 徳蔵

    全日本鍼灸学会雑誌 = Journal of the Japan Society of Acupuncture and Moxibustion ( 全日本鍼灸学会 )  66 ( 4 ) 264 - 281  2016.11

    CiNii

  • Information and Real Sensor Network Supported Intelligent Environment : New Concepts of Information and "Info-Medicine"

    TATSUMI Haruyuki, MIZOGUCHI Shogo, SHIMMI Takahiko, OTA Syuzo, NINOMIYA Takafumi, ICHIKAWA Ryoichi, KIKUCHI Shin

    The Journal of the Institute of Electronics, Information, and Communication Engineers ( The Institute of Electronics, Information and Communication Engineers )  97 ( 8 ) 695 - 701  2014.08

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    46億年ものノウハウを蓄えている生命の基本単位である細胞や人体の研究から,知的環境を支えるリアルセンサネットワークとして,ユビキタスゼロクリックセンサネットワーク(Ubiquitous Zero-Click Sensor Network)を提案し実証実験を行ってきた.そこから情報が薬として作用していることを見いだし,「情報薬」(Info-Medicine)という新しい概念を作り出した.また,細胞生物学・情報社会科学的観点から「情報」を定義することにより,「情報薬」の可能性が更に広がった.身体はすばらしいリアルセンサネットワークそのもので,あらゆるTo-Brain Type(II型)情報薬を得て生命活動に活用している.多くの情報薬の中から取捨選択し,あるものはIn-Brain Type(III型)情報薬として作用している.これらはIn-Social Type(I型)情報薬の影響を受け,更に意識と無意識によりTo-Cellular Type(IV型),そしてIn-Cellular Type(V型)情報薬が産生され,健康を保っている.特に意識に上らない自動コントロールの破綻,あるいは,意識されても適切な対策がなされないことが病気につながる.そこで,ユビキタスゼロクリックセンサネットワークにより察知し,それを事前に防ごうとするのが,戦略的防衛医療構想(SDMCI : Strategic Defensive Medical Care Initiative)で,その強力な武器は「情報薬」である.

    CiNii

  • 健康増進への新しい展開 : 医学と情報科学の融合 : 戦略的防衛医療構想 :「情報薬」による超予防医療

    辰巳 治之, 新見 隆彦, 太田 秀造, 溝口 照悟, 菊池 真, 市川 量一, 二宮 孝文, 中村 正弘

    バイオメカニズム学会誌 = Journal of the Society of Biomechanisms ( バイオメカニズム学会 )  35 ( 2 ) 113 - 119  2011.05

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    戦略防衛構想(SDI : Strategic Defense Initiative) では，IT をフル利活用しミサイルが飛んで来るのを逸早く察知して，その軌道を綿密にすばやく計算し，タイミングよく空中で破壊する。このことにより積極的な攻撃は行わず，究極の防衛を実現している。このことにヒントを得て，医療系で実現しようというものが，我々の提案している戦略的防衛医療構想(SDMCI :Strategic Defensive Medica1-Care Initiative) である。 超予防医療としてのこの構想は，Ver.1.0 から始まり，現在では，Ver.3.0 に達している。これらを推進し実現する為の強力な武器は「情報薬」で，IT 及び情報科学との融合が，これからの21 世紀の医療には必須のものとなる。その要素としてのゼロクリック，どこでも逆ナースコール，そして，ユビキタスセンサーネットワークの解説と、その応用例を示した。

    DOI CiNii

  • Studies of the length of myelin internodes of cultured rat dorsal root ganglia cells infected by adenovirus with wild type and mutated (689 ins T) aprataxin cDNA

    堀本 佳誉, 菊池 真, 舘 延忠

    札幌医科大学保健医療学部紀要 = Bulletin of School of Health Sciences Sapporo Medical University ( 札幌医科大学保健医療学部 )  0 ( 13 ) 21 - 27  2011.03

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    眼球運動失行を伴う失調症（AOA1）はaprataxin遺伝子の変異により起こる疾患である。本研究では、アデノウイルスを用いて野生型 aprataxin cDNA、689insT変異型aprataxin cDNA、LacZを発現するcDNAのそれぞれを培養ラット末梢髄鞘に導入したもの（Wild, Mt, LacZ）と導入しない培養ラット末梢髄鞘（NC）を作製・培養し、絞輪間距離の計測を行った。遺伝子導入後、Wild、Mt、LacZ、NCの4群間における絞輪間距離の比較ではNCとWildの間（P<0.O1）、LacZとWildの間（P<0.001）に有意差を認め、Mtは他の3群と有意差を認めなかった。この結果から、末梢神経細胞に対してMtの機能は優性阻害の影響はなく機能の喪失であり、Wildで起こるaprataxinの過剰な発現は、Schwann細胞の配列後に起こる伸長や、髄鞘化の開始、軸索の伸長に何らかの影響を及ぼす可能性が推測された。

    DOI CiNii

  • A study of cultured rat dorsal root ganglia cells infected with a recombinant adenovirus containing mutant MPZ cDNA in myelination

    菊池 真, 小塚 直樹, 二宮 孝文

    札幌医科大学保健医療学部紀要 = Bulletin of School of Health Sciences Sapporo Medical University ( 札幌医科大学保健医療学部 )  0 ( 13 ) 13 - 20  2011.03

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    Myelin Protein Zero(MPZ)遺伝子の変異はCharcot-Marie-Tooth病を引き起こす．今回，我々は，ラット後根神経節細胞由来の培養細胞に389A>G(130Lys>Arg)の点変異を有するMPZ cDNAを導入し，その形態学的観察を行った．培養後，2週間の時点で、アデノウイルスベクターを用い，野生型MPz cDNA(wild)，点変異MPZ cDNA(Mt)，LacZ cDNA(LacZ)のそれぞれを導入した．同時に，何も導入しない群(NC)も作成した．cDNA導入後，さらに2週間の培養を継続し，合計4週間の培養を行った．解析は免疫組織化学染色法と髄節長の計測，および電子顕微鏡による微細構造の観察を行った．結果，アデノウイルスベクターを用いて，培養細胞にMPZ cDNAの導入が可能であった．また，全ての群間において髄節長に違いはみられなかった．また，電子顕微鏡による観察でも違いはみられなかった．これらのことから，389A>G(130Lys>Arg)の点変異をもつMPZ遺伝子は2週間の培養では髄鞘の形態に作用しないことが考えられた．しかし，今後，髄鞘の病理学的変化がいつの時点であらわれるかについて，DRGの長期培養も含めた更なる実験が必要であると考えられた。

    DOI CiNii

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Research Projects 【 display / non-display 】

  • IL-6による分化PC12細胞の保護機能の解明

    基盤研究(C)

    Project Year :

    2022.04
    -
    2025.03
     

    菊池 真

  • 低酸素・低グルコース下における末梢神経軸索内ミトコンドリアの動態解析

    基盤研究(C)

    Project Year :

    2018.04
    -
    2023.03
     

    菊池 真

    　View Summary

    R3年度が最終年度であったが、論文執筆に時間がかかり、研究期間の延長を申請した。 低酸素・低グルコース(OGD)による神経軸索内ミトコンドリアの動態解析を行った。その結果、OGD暴露１時間後に輸送ミトコンドリアの数が優位に減少し、その後、停留ミトコンドリアの長さが短くなった。停留ミトコンドリアの長さが短くなった原因としては、①輸送ミトコンドリアの軸索内での停止、②停留ミトコンドリアの分裂(fusion)、③停留ミトコンドリア自体の長さの短縮がみられた。 電子顕微鏡による観察では球状ミトコンドリアの数が優位に増加しているのが観察された。 これらの結果より、OGDの暴露は神経軸索内のミトコンドリアの輸送を阻害し、加えてミトコンドリアの分裂および停留ミトコンドリア自身の短縮を誘導することにより、本来、筒状の軸索内ミトコンドリアを球状にすることが分かった。また、これらの現象はアポトーシスやネクローシス、軸索変性などが観察される前に観察された。 これらの事より、OGDにより誘導される軸索内ミトコンドリアの変化は、神経細胞死に先立って観察されることが明らかとなり、末梢循環障害などによる神経細胞変性の治療ターゲットとして、ミトコンドリアが関与する可能性が示唆された。

  • Effect of hypoxia to axonal mitochondria in cultured dorsal root ganglion cells of rat

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2015.04
    -
    2019.03
     

    Kikuchi Shin

    　View Summary

    Hypoxia induces neuronal death in vivo. Mitochondria consume oxygen and produce ATP in living cell. In this study, we investigated the motility of axonal mitochondria under hypoxia. We used cultured dorsal root ganglion cells of rat and marked mitochondria in the axon with fluorescent protein by genetic engneering technique. The rate of motile mitochondria in axon under hypoxia showed no difference between contral. In addition, we investigated motile mitochondria in axon under glucose-oxygen deprivation (OGD) for 24 hours. OGD decreased the number of motile mitochondria in axons. Our results suggeted that motility of mitochondria is not controlled by hypoxia only, but by complex mechanisms such as OGD.

  • Pseudo-ischemia induced axonal mitochondria changes in cultured dorsal root ganglion neurons

    Grant-in-Aid for Young Scientists (B)

    Project Year :

    2013.04
    -
    2016.03
     

    Kikuchi Shin

    　View Summary

    In this study, we investigated that the effects of cobalt, considered to an inducer of hypoxia-inducible factor-1a (HIF-1a), on the axonal degeneration and mitochondrial dynamics in cultured peripheral nervous axons. Twenty-four hours exposure of cobalt decreased the rate of the motile mitochondria in the axons. Of particular note, the 800μM cobalt density suppressed the axonal mitochondria transport completely. The observation of microstructure with the transmission electron microscope found that high density cobalt destroyed the architecture of axonal mitochondria. In the axons treated with cobalt, the number of axonal swelling was associated with the increase of cobalt concentration. Although the mechanisms of neurotoxicity induced by cobalt are not clear, our results showed that high cobalt concentrations reduced mitochondria transport and induced axonal degeneration.

  • Treatment of sodium valproate and amantazine hydrochloride in spinal muscular atrophy

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2010
    -
    2012
     

    TACHI Nobutada, YAMASITA Tosiharu, KIKUCHI Sin, OHYA Kazuhiro

    　View Summary

    Spinal muscular atrophy (SMA) is characterized by degeneration of the motoric neurons of the anterior horn cells of the spinal cord, leading to muscle atrophydue to mutation of telomeric survival motor neuron (SMN1) located in chromosome on 5q13. SMN2, high homology of SMN1, is determined to disease severity. SMA II and III have 3 or 4 numbers of SMN2 gene. Recently, sodium valproate (VPA) treated with epilepsy, increased number of SMN2 gene in vitro. Increased muscle strength with Amantazine treatment has reported in SMA II patients. We studied effect of treatment with VPA and amantazine using ccultured skin fibroblasts derived from SMA patints based on SMN mRNA and protein levels. Results: VPA treatment was effective but Amantazine was no effeitve in vitro.

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