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Effects of herpes simplex virus vectors encoding poreless TRPV1 or protein phosphatase 1α in a rat cystitis model induced by hydrogen peroxide

Gene Therapy volume 25, pages 20–26 (2018)Cite this article

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Abstract

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, PL or PP1α were inoculated into the bladder wall of female rats. After 1 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 nerve growth factor 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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Acknowledgements

This work was financially supported by the Department of Defense (W81XWH-12-1-0565) and National Institutes of Health (DK088836).

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Authors and Affiliations

  1. Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    S Takai, T Majima, P Tyagi & N Yoshimura

  2. Department of Microbiology & Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    B Reinhart, W F Goins & J C Glorioso

  3. Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    S Takai, T Majima, Y Funahashi & M Gotoh

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  1. S Takai
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  2. T Majima
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  4. W F Goins
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  6. M Gotoh
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  7. P Tyagi
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  8. J C Glorioso
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  9. N Yoshimura
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Correspondence to N Yoshimura.

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Takai, S., Majima, T., Reinhart, B. et al. Effects of herpes simplex virus vectors encoding poreless TRPV1 or protein phosphatase 1α in a rat cystitis model induced by hydrogen peroxide. Gene Ther 25, 20–26 (2018). https://doi.org/10.1038/gt.2017.94

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