NLRP3/IL1β inflammasome associated with the aging bladder triggers bladder dysfunction in female rats

Chen,Lin; He,Ping‑Lin; Yang,Jin; Yang,Ya‑Fei; Wang,Kai; Amend,Bastian; Stenzl,Arnulf; Zhang,Ya‑Mei; Wang,Zi‑Li; Xing,Sha‑Sha; Luo,Xu

doi:10.3892/mmr.2019.9919

NLRP3/IL1β inflammasome associated with the aging bladder triggers bladder dysfunction in female rats

Authors:
- Lin Chen
- Ping‑Lin He
- Jin Yang
- Ya‑Fei Yang
- Kai Wang
- Bastian Amend
- Arnulf Stenzl
- Ya‑Mei Zhang
- Zi‑Li Wang
- Sha‑Sha Xing
- Xu Luo
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Affiliations: Department of Urology, Affiliated Hospital of Chengdu University, Chengdu, Sichuan 610000, P.R. China, Department of Urology, University of Tübingen, D-72074 Tübingen, Germany, Central Laboratory, Affiliated Hospital of Chengdu University, Chengdu, Sichuan 610000, P.R. China, Department of Urology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563003, P.R. China
Published online on: January 31, 2019 https://doi.org/10.3892/mmr.2019.9919
Pages: 2960-2968
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bladder dysfunction is associated with fibrosis‑mediated aging, but the corresponding mechanism remains to be elucidated. Activation of the NACHT, LRR and PYD domains‑containing protein 3 (NLRP3) inflammasome is related to chronic diseases associated with aging, including organ fibrosis. The present study aimed to explore the role of NLRP3/interleukin 1β in aging‑associated bladder dysfunction. Female Sprague‑Dawley rats were divided into the following two groups (n=10 rats/group): 2‑month‑old group (young group) and 24‑month‑old group (old group). Urodynamics were performed to assess the bladder function of the rats. The histological alterations were identified using Masson's trichrome staining. The protein expression of the NLRP3 inflammasome and NAD‑dependent protein deacetylase sirtuin‑3, mitochondrial (SIRT3) were detected by western blot analysis, and immunohistochemistry was used to examine a senescence marker (p21) and the NLRP3 inflammasome in the bladder. The localization of the key molecule Caspase1 was determined using immunofluorescence. The voiding time was longer in the old group compared with the young group. The expression levels of SIRT3 were reduced in the bladders of the old group, while those of the NLRP3 inflammasome and the senescence marker were significantly higher in the bladders of the old group compared with the young group. Increased collagen deposition leads to chronic bladder fibrosis with increased NLRP3. In the histological examination, the bladders of the old group displayed increased collagen deposition, urothelial thinning and detrusor shrinkage compared with the young group. Tissue fibrosis and urothelial alterations are the principal causes of bladder dysfunction during aging. Downregulated SIRT3 and upregulated expression of the NLRP3 inflammasome are involved in the degradation of aging bladders. Inflamm‑aging is a novel mechanism underlying bladder dysfunction.

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