Effects of herpes simplex virus vectors encoding poreless TRPV1 or protein phosphatase 1α in a rat cystitis model induced by hydrogen peroxide.
Effects of herpes simplex virus vectors encoding poreless TRPV1 or protein phosphatase 1α in a rat cystitis model induced by hydrogen peroxide.
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DOI：
10.1038/gt.2017.94
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发表时间：
2018-01
期刊：
影响因子：
5.1
通讯作者：
Yoshimura N
中科院分区：
文献类型：
--
作者：
Takai S;Majima T;Reinhart B;Goins WF;Funahashi Y;Gotoh M;Tyagi P;Glorioso JC;Yoshimura N
传入兴奋性增强被认为是间质性膀胱炎/膀胱痛综合征（IC/BPS）的重要病理生理基础。此外，已知瞬时受体电位香草素-1 （TRPV1）受体参与传入致敏。过氧化氢（HP）诱导的膀胱炎动物已被用作显示膀胱慢性炎症病理特征的模型。本研究利用hp诱导的大鼠膀胱炎模型，研究了复制缺陷型单纯疱疹病毒（HSV）载体编码无孔TRPV1 （PL）或TRPV1负调节因子蛋白磷酸酶1α (PP1α)的基因治疗效果。将编码绿色荧光蛋白（GFP）、PL或PP1α的HSV载体接种于雌性大鼠膀胱壁上。1周后，1% HP或生理盐水进入膀胱，2周后进行病毒接种评估。在hp诱导的膀胱炎大鼠中，PL或PP1α基因的传递减少了疼痛行为，并缩短了收缩间期。此外，两种治疗方法均可降低膀胱粘膜中NGF的表达，减轻以炎症细胞浸润为特征的膀胱炎症，并增加膀胱重量。综上所述，单纯疱疹病毒介导的靶向TRPV1受体的基因治疗可有效治疗IC/BPS。
Enhanced afferent excitability is considered to be an important pathophysiological basis of interstitial cystitis/bladder pain syndrome (IC/BPS). In addition, transient receptor potential vanilloid-1 (TRPV1) receptors are known to be involved in afferent sensitization. Animals with hydrogen peroxide (HP)-induced cystitis have been used as a model exhibiting pathologic characteristics of chronic inflammatory condition of the bladder. This study investigated the effect of gene therapy with replication-defective herpes simplex virus (HSV) vectors encoding poreless TRPV1 (PL) or protein phosphatase 1 α (PP1α), a negative regulator of TRPV1, using a HP-induced rat model of cystitis. HSV vectors encoding green fluorescent protein (GFP), PL or PP1α were inoculated into the bladder wall of female rats. After one week, 1% HP or normal saline was administered into the bladder, and the evaluations were performed 2 weeks after viral inoculation. In HP-induced cystitis rats, gene delivery of PL or PP1α decreased pain behavior as well as a reduction in the intercontraction interval. Also, both treatments reduced NGF expression in the bladder mucosa, reduced bladder inflammation characterized by infiltration of inflammatory cells, and increased bladder weight. Taken together, HSV-mediated gene therapy targeting TRPV1 receptors could be effective for the treatment of IC/BPS.
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影响因子：
4.2
作者：
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通讯作者：
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影响因子：
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作者：
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Yoshimura, Naoki
影响因子：
5.3
作者：
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通讯作者：
Ferrer-Montiel, A