Study in gene therapy for lower urinary tract dysfunction

下尿路功能障碍基因治疗研究

基本信息

  • 批准号:
    14571507
  • 负责人:
  • 金额:
    $ 2.18万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2002
  • 资助国家:
    日本
  • 起止时间:
    2002 至 2004
  • 项目状态:
    已结题

项目摘要

Background : Muscarinic M3(M3) receptor has been recognized as a major muscarinic receptor for smooth muscle contractions of the urinary bladder. Nitric oxide(NO) is one of the important relaxing factor in bladder. Under the hypothesis that overexpression of nNOS and M3 receptor in the bladder would inhibition and enhancement of bladder contractions, respectively. So, we have transferred the nNOS and M3 receptor gene into rat bladders using electroporation(EP) and evaluated the functional expression of the gene.Methods : Plasmids expressing luciferase, GFP, nNOS and M3 receptor were injected into the rat bladder and square-wave electric pulses were immediately applied. Two days after gene transfer, we analyzed gene expression. Immunohistochemical staining for nNOS and M3 receptors was performed and the contractile responses from isolated bladder strips, which were carbachol and electrical field stimulation(EFS), were evaluated. NO released from isolated bladder strips was also assessed … More using microdialysis and HPLC. M3 gene transfer also preformed into bladder of deneravation(detrusor underactivity) model rat.Results : The optimal conditions of electroporation were 8 pulses, 45 voltages, 50 millisec/pulses and 1 Hz. Under these conditions, luciferase gene expression was enhanced approximately 300-fold, compared to an injection of DNA only. Regarding immunohistochemistry with an anti-nNOS and anti-M3 receptor, increases in immunoactivity wer observed in the nNOS and M3 receptor gene transferred rat bladder, compared to the bladder of the control rat. In rats with the nNOS gene injected by electroporation there was marked nNOS immunoreactivity, and NOx released from bladder strips was significantly greater than in the control groups. In rats with the transferred M3 receptor gene, carbachol- and EFS-induced maximum responses of bladder smooth muscle strips significantly increased. In the M3 receptor transferred denervation rats, detrusor contractility for carbachol and EFS significantly increased, as compared with the control rats. The cystometric findings showed, decreased micturituion interval and increased in bladder pressure.Conclusions : These findings suggest that an in vivo EP procedure is a useful method for gene transfer into the bladder. nNOS gene transferred by this procedure functionally expresses and contributes to NO production, and that an overexpression of M3 receptor in the rat bladder enhances bladder contractility. This technique may become a new treatment modality for detrusor underactivity. Less
研究背景:毒蕈碱M3受体(M3 receptor)是膀胱平滑肌收缩的主要受体。一氧化氮(NO)是膀胱重要的舒张因子之一。假设nNOS和M3受体在膀胱中的过表达分别抑制和增强膀胱收缩。因此,我们采用电穿孔法将nNOS和M3受体基因导入大鼠膀胱,并对其功能表达进行了研究。方法:将表达荧光素酶、绿色荧光蛋白(GFP)、nNOS和M3受体的质粒分别注入大鼠膀胱,并立即施加方波电脉冲。基因转移后两天,我们分析了基因表达。采用nNOS和M3受体免疫组化染色,观察氨甲酰胆碱(carbachol)和电场刺激(EFS)对离体膀胱肌条收缩反应的影响。还评估了从离体膀胱条释放的NO ...更多信息 采用微透析和HPLC。结果:电穿孔的最佳条件为:脉冲数8,电压45,脉冲数50毫秒,频率1 Hz。在这些条件下,与仅注射DNA相比,荧光素酶基因表达增强约300倍。关于用抗nNOS和抗M3受体的免疫组织化学,与对照大鼠的膀胱相比,在nNOS和M3受体基因转移的大鼠膀胱中观察到免疫活性增加。在大鼠与nNOS基因注射电穿孔有显着的nNOS免疫反应,和NOx释放的膀胱条显着大于对照组。在转移M3受体基因的大鼠中,卡巴胆碱和EFS诱导的膀胱平滑肌条的最大反应显着增加。与对照组相比,M3受体转移去神经大鼠的逼尿肌对卡巴胆碱的收缩力和EFS显著增加。膀胱测压结果显示,排尿间隔缩短,膀胱压力增加。结论:这些结果表明,在体内EP程序是一种有用的方法,基因转移到膀胱。通过该方法转移的nNOS基因功能性地表达并有助于NO的产生,并且大鼠膀胱中M3受体的过表达增强膀胱收缩性。该技术有望成为治疗逼尿肌功能不全的一种新方法。少

项目成果

期刊论文数量(44)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
吉田正貴他: "神経因性膀胱の平滑筋収縮機構"脳21. 5・3. 283-287 (2002)
Masaki Yoshida 等:“神经源性膀胱的平滑肌收缩机制” Brain 21. 5, 3. 283-287 (2002)
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
In vivo muscarinic m3 receptor gene transfer into rat bladder smooth muscle by electroporation
通过电穿孔将体内毒蕈碱 m3 受体基因转移至大鼠膀胱平滑肌
  • DOI:
  • 发表时间:
    2002
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Yamanishi;T et al.;Kamai T et al.;M.Yoshida et al.
  • 通讯作者:
    M.Yoshida et al.
過活動膀胱のEBMに基づいた治療
基于 EBM 的膀胱过度活动症治疗
  • DOI:
  • 发表时间:
    2004
  • 期刊:
  • 影响因子:
    0
  • 作者:
    吉田正貴;他
  • 通讯作者:
J.Bade, O.Ishizuka, M.Yoshida: "Future research needs for the definition/diagnosis of interstitial cystitis"International Journal of Urology. 10. S31-S34 (2003)
J.Bade、O.Ishizuka、M.Yoshida:“间质性膀胱炎的定义/诊断的未来研究需求”国际泌尿外科杂志。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
吉田正貴他: "排尿障害に対する遺伝子治療の開発"西日本泌尿器科. 63・5. 331-338 (2001)
Masataka Yoshida 等:“泌尿系统疾病基因治疗的发展” 西日本泌尿外科 63・5(2001 年)。
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    0
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YOSHIDA Masaki其他文献

Association between Odor Memory and Prefrontal Cortex : An fMRI Study [Presidential Award Proceedings]
气味记忆与前额皮质之间的关联:功能磁共振成像研究 [总统奖论文集]
  • DOI:
    10.2463/jjmrm.2018-1662
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    MASAOKA Yuri;WATANABE Keiko;IDA Masahiro;YOSHIDA Masaki;KOIWA Nobuyoshi;YOSHIKAWA Akira;KUBOTA Satomi;IIZUKA Natsuko;KAWAMURA Mitsuru;ONO Kenjiro;IZUMIZAKI Masahiko
  • 通讯作者:
    IZUMIZAKI Masahiko

YOSHIDA Masaki的其他文献

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{{ truncateString('YOSHIDA Masaki', 18)}}的其他基金

Ethical Research on the Principle of the Coexistence of Kami, Buddhism, and Heaven: Clarification of the Axis of Japanese Thought
神、佛、天并存原理的伦理研究:澄清日本思想轴心
  • 批准号:
    20K00038
  • 财政年份:
    2020
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Development of small molecule activation systems based on the photoexcitation of metal complexes
基于金属配合物光激发的小分子活化系统的开发
  • 批准号:
    25888023
  • 财政年份:
    2013
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Research Activity Start-up
Study for immortalization of human bladder smooth muscle cells
人膀​​胱平滑肌细胞永生化的研究
  • 批准号:
    25462531
  • 财政年份:
    2013
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Studies on the thermal and mechanical interaction between the supercontinent cycle and mantle convection using numerical models
利用数值模型研究超大陆旋回与地幔对流之间的热力和机械相互作用
  • 批准号:
    23340132
  • 财政年份:
    2011
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Cell cycle and organelle specific proteomic analysis of eukaryotic cell
真核细胞的细胞周期和细胞器特异性蛋白质组学分析
  • 批准号:
    23770234
  • 财政年份:
    2011
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Numerical studies on generation mechanism of plume-mode and plate-mode by three-dimensional mantle convection models
三维地幔对流模型羽流模式和板块模式生成机制的数值研究
  • 批准号:
    20740260
  • 财政年份:
    2008
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Study of the idea of "the dead" from a viewpoint of Japanese history of ethical thoughts
日本伦理思想史视域中的“死者”观念研究
  • 批准号:
    20720005
  • 财政年份:
    2008
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Study in the pathophysiology of overactive bladder-Effects of bladder ischemia and hyperlipidemia
膀胱过度活动症的病理生理学研究-膀胱缺血和高脂血症的影响
  • 批准号:
    18591759
  • 财政年份:
    2006
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Development of biomimetic prosthesic hand with sensory aid
具有感觉辅助的仿生假手的开发
  • 批准号:
    12558113
  • 财政年份:
    2000
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Study in the role of nitric oxide (NO) and advanced glycation end products (AGE) on bladder function
一氧化氮(NO)和晚期糖基化终产物(AGE)对膀胱功能作用的研究
  • 批准号:
    11671563
  • 财政年份:
    1999
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

相似海外基金

Preclinical gene therapy for genetic urinary bladder disease
遗传性膀胱疾病的临床前基因治疗
  • 批准号:
    MR/T016809/1
  • 财政年份:
    2020
  • 资助金额:
    $ 2.18万
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    Research Grant
Development of invasive bladder cancer gene therapy focusing on genomic instability
专注于基因组不稳定性的侵袭性膀胱癌基因治疗的发展
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    20K18096
  • 财政年份:
    2020
  • 资助金额:
    $ 2.18万
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    Grant-in-Aid for Early-Career Scientists
Development of gene therapy for invasive bladder cancer focusing on genomic instability
专注于基因组不稳定性的侵袭性膀胱癌基因治疗的开发
  • 批准号:
    17K11154
  • 财政年份:
    2017
  • 资助金额:
    $ 2.18万
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    Grant-in-Aid for Scientific Research (C)
Combination chemo-siRNA gene therapy of nonmuscle-invading bladder cancer
非肌肉侵袭性膀胱癌的联合化疗-siRNA 基因治疗
  • 批准号:
    8121224
  • 财政年份:
    2012
  • 资助金额:
    $ 2.18万
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Liposomal IL-21/IL-15 Gene Therapy in an Orthotopic Bladder Cancer Model and Prevention of Tumor Invasion and Metastasis
原位膀胱癌模型中的脂质体IL-21/IL-15基因治疗及预防肿瘤侵袭和转移
  • 批准号:
    23791788
  • 财政年份:
    2011
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Liposomal PTEN Gene Therapy in an Orthotopic Bladder Cancer Modeland Prevention of Tumor Invasion and Metastasis
原位膀胱癌模型中的脂质体PTEN基因治疗及预防肿瘤侵袭和转移
  • 批准号:
    23791786
  • 财政年份:
    2011
  • 资助金额:
    $ 2.18万
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    Grant-in-Aid for Young Scientists (B)
Intravesical Gene Therapy for BCG Refractory Bladder Cancer
卡介苗难治性膀胱癌膀胱内基因治疗
  • 批准号:
    8230256
  • 财政年份:
    2011
  • 资助金额:
    $ 2.18万
  • 项目类别:
The effect of TS-1 and enhanced chemosensitivity to TS-1 by rTS gene therapy in bladder cancer.
膀胱癌中 TS-1 的作用以及 rTS 基因治疗对 TS-1 化疗敏感性的增强。
  • 批准号:
    21791529
  • 财政年份:
    2009
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Improving Gene Therapy for Superficial Bladder Cancer
改善浅表性膀胱癌的基因治疗
  • 批准号:
    7729508
  • 财政年份:
    2008
  • 资助金额:
    $ 2.18万
  • 项目类别:
Liposomal Interleukin-15 Gene Therapy in an Orthotopic Bladder Cancer Model and Acquirement of Immunologic Memory
原位膀胱癌模型中的脂质体白介素 15 基因治疗和免疫记忆的获得
  • 批准号:
    20791121
  • 财政年份:
    2008
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
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