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SHIBATA Yasuhiro

    Graduate School of Medical Sciences Department of Anatomy and Neuroscience　Lecturer
Last Updated :2025/04/29

Researcher Information

URL

J-Global ID

Research Areas

  • Life sciences / Anatomy
  • Life sciences / Urology

Academic & Professional Experience

  • 2014  Nagoya City University医学(系)研究科(研究院)助教

Association Memberships

  • The Japanese Society for Neurochemistry   The Japan Neuroscience Society   The Japanese Association of Anatomists   日本泌尿器科学会   

Published Papers

MISC

Research Grants & Projects

  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2024/04 -2028/03 
    Author : 岩田 宏満; 柴田 泰宏; 加藤 洋一; 鵜川 眞也; 粂 和彦; 歳藤 利行; 冨田 淳; 嶋田 逸誠; 荻野 浩幸; 平山 亮一
  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2022/04 -2027/03 
    Author : 鵜川 眞也; 岩崎 真一; 柴田 泰宏; 島田 昌一; 熊本 奈都子; 村上 信五; 植田 高史
  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2019/04 -2023/03 
    Author : 柴田 泰宏; 鵜川 眞也; 窪田 泰江; 太田 裕也
     
    過活動膀胱や神経因性膀胱における頻尿を抑制するための薬剤には抗コリン薬およびβ3受容体作動薬などが使用されている。しかし、いずれの薬剤も排尿筋上の受容体をターゲットとしており、膀胱の伸展刺激を受容して尿意の起点となるであろう膀胱の感覚神経をターゲットとした薬剤は未だに無い。これは尿意を受容する本態として想定されている機械刺激受容について不明な点が多いためである。これらを明らかにするため、私たちは線虫の機械刺激受容体の哺乳類ホモログであるASICファミリーに注目し、ASICファミリーのノックアウトマウスおよびノックインマウスを用いてその膀胱における分布と機能の詳細を検討することを計画した。私たちは、ASIC4が排尿機能に与える影響を観察するため、ASIC4ノックアウトマウスを用いたvoid spot assayによる排尿行動解析を行った。生理的条件下において、８週齢から１２週齢の野生型マウスおよびASIC4ノックアウトマウスの比較を行ったところ、ノックアウトマウスではプライマリースポット面積が小さくなる傾向があること、またスポット数が増大する傾向にあることから、野生型マウスと比較してASIC4ノックアウトマウスの最大膀胱容量は小さく、また頻尿を呈していることが示唆された。また、当研究室でまだ得られていないASIC2ノックインマウスおよびAISC2ノックアウトマウスをCRISPR/Cas9システムを用いて作出するための準備として、off-targetの少ないgRNAのベクターを設計するとともに、ノックインマウス作出のための遺伝子供与ベクターの設計を行った。相同アーム長は1kbp、ノックインに用いるTag配列はVSV-G配列を用いることとした。現在、本学の実験動物研究教育センターと協力し、次年度に繰り越した予算にて動物の作出を計画している。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2017/04 -2021/03 
    Author : Ugawa Shinya
     
    ASICs (acid-sensing ion channels) are putative mechano-gated cation channels in mammals. In the present study, we discovered that at least ASIC1a, ASIC1b, and ASIC4 are expressed in mouse auditory and vestibular hair cells. In particular, transmission electron microscopy revealed that ASIC1b proteins were located at the stereociliary tips, suggesting that all the three ASIC subtypes are somehow involved in the generation of mechanoelectrical transduction (MET) currents. ABR (auditory brainstem response) tests demonstrated the slight-to-moderate degree of deafness in ASIC1b or ASIC4 knockout mice. Further investigations are needed to assess the physiological roles of ASICs in mouse inner ear MET.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2016/04 -2020/03 
    Author : Shibata Yasuhiro
     
    There are many patients suffering from overactive bladder, and the overall picture of the mechanism of acceptance of urination is largely unknown. We have focused on the acid-sensitive ion channel family, which is a mechanostimulatory receptor candidate gene. Among them, the ASIC4 gene is expressed in the bladder smooth muscle layer, and the ASIC4 mediated influx current is calibrated by an osmotic pressure change, which is a kind of mechanical stimulation in the expression system using Xenopus oocytes. I found a thing. From this, it was speculated that ASIC4 plays a some sort of role in mechanical stimulation reception in the bladder.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2017/06 -2019/03 
    Author : Ugawa Shinya
     
    We identified a putative mechanosensory channel ASIC-X in mouse auditory hair cells, and explored its channel properties using a combination of electrophysiology and ratio-imaging techniques with fura-2 and SBFI. Although the leakage currents of heterologously expressed ASIC-X were augmented by strong shear stress, neither hypotonicity nor direct stretching of plasma membrane enhanced the currents. Mechanoelectrical transduction (MET) currents in outer hair cells (OHCs) of ASIC-X knockout mice did not significantly change in the amplitude, compared to MET currents in wild-type OHCs, which is in good agreement with the in vitro data. However, our investigations revealed that the ASIC-X channel was selective to sodium ions. Therefore, ASIC-X is most likely to function as a sodium leak channel in vivo rather than as a mechanosensitive molecule. The tissue distribution of the channel should be clarified in detail next.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2015/04 -2019/03 
    Author : UEDA Takashi; TSUSHIMA Hiromi
     
    Acid-sensing ion channel 1a (ASIC1a) was primarily detected in P2X2/P2X3-immunopositive nerve fibers within mouse taste buds, but not in mouse taste receptor cells. In primary culture of neurons isolated from geniculate ganglia, proton differentially modulated ATP-induced intracellular calcium mobilization. In a heterologous expression system using recombinant P2X2, P2X3 and ASIC1a, acidic buffer (pH6.5) enhanced P2X2/P2X3-mediated calcium response, while it reduced P2X3-mediated cellular response. ASIC1a further modulated proton-induced modification of P2X2/P2X3-mediated response. Finally, ASIC1a-knockout mice show reduced behavioral response to sour tastants (citric and hydrochloric acids). Proton could thus be a neuromodulator for sour taste perception and ASIC1a in the P2X2/P2X3-positive gustatory neurons may be involved in this signaling pathway.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2014/04 -2017/03 
    Author : SHIBATA Yasuhiro; SASAKI Shoichi; UGAWA Shinya
     
    Although benign prostate hyperplasia (BPH) is common disease, the cause of BPH is still unclear. To investigate the mechanism of BPH development, we use the novel BPH model which was made by implanting the urogenital sinus of neonatal rats to sub-capsule of the prostate of adult male rats. Using this model we discovered the grail-cell derived neurotrophic factor (GDNF) expresses in interstitial cell. And we demonstrate that GDNF increase the growth rate of human prostate interstitial cell-line, and RET signal cascade was related with prostate volume positively in human BPH tissue.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2013/04 -2016/03 
    Author : Takada Masa; KUBOTA Yasue; IMURA Makoto; SHIBATA Yasuhiro; KOHRI Kenjiro; SASAKI Shoichi; KOJIMA Yoshiyuki
     
    Benign prostate hyperplasia is a non-cancerous enlargement of the prostate which cause lower urinary tract symptoms, such as urinary frequency, urinary urgency interrupted urine stream and so on. Aging society increase the BPH prevalence and these symptoms degrade the quality of life. Although BPH is common, the cause of BPH is still unclear. To investigate the mechanism of BPH development, we use the novel BPH model which was made by implanting the urogenital sinus of neonatal rats to sub-capsule of the prostate of adult male rats. Using this model we discovered the grail-cell derived neurotrophic factor (GDNF) plays the important role in interstitial cell proliferation. In this study, we demonstrate the GDNF increase the growth rate of human prostate interstitial cell line, and in these cell line signal cascade such as RET phosphorylation pathway and GZF1 were activated.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2013/04 -2016/03 
    Author : Kubota Yasue; SASAKI Shoichi; HAMAKAWA Takashi; SIBATA Yasuhiro; IMURA Makoto; TAKADA Masa; KOHRI Kenjiro
     
    In the gastrointestinal tract, interstitial cells of Cajal (ICCs) act as primary pacemaker cells to generate slow wave activity, and play a fundamental role in the transmission of signals from enteric neurons to smooth muscle cells. ICCs have been also identified in the urinary bladder. KIT is used as an identification marker of ICCs, and KIT-positive ICCs are located throughout the bladder wall. They may be involved in signal transmission between smooth muscle bundles, from efferent nerves to smooth muscles, and from urothelium to afferent nerves. Not only disturbance of spontaneous contractility caused by the altered dertusor ICC signal transduction between nerves and smooth muscle cells but also disturbance of signal transduction between urothelial cells and sensory nerves via suburethelial ICC may induce overactive bladder (OAB). The blockage of c-kit receptor may offer a new therapeutic strategy for OAB treatment, although further study will be needed.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2012/04 -2014/03 
    Author : SHIBATA Yasuhiro; SASAKI Shoichi; UGAWA Shinya; HAMAKAWA Takashi; KOJIMA Yoshiyuki; KOHRI Kenjiro
     
    In order to reveal the mechanism of urinary urgency evoked by cold sensation, we investigated the convergence of the primary sensory afferents of the skin and bladder. Dichotomizing afferents of L6-S1 dorsal root ganglion neurons that innervate the skin and bladder was constantly observed with retrograde neuron tracers in rats. In-situ hybridization revealed that approximately 8.0% of the double-labelled cells expressed transient receptor potential channel melastatin member 8 (TRPM8) transcripts in the dorsal root ganglions. Cold and menthol stimuli to the skin generated bladder nerve responses conducted through dichotomizing axons, which significantly decreased in the presence of the TRPM8 blocker BCTC. In conclusion, TRPM8-expressing sensory neurons with dichotomizing axons projecting to the skin and bladder may be responsible for the urinary urgency evoked by cold sensation.

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