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International Urology and Nephrology

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Open Access 18-08-2023 | Cystitis | Urology - Original Paper

Serpina3n/serpina3 alleviates cyclophosphamide-induced interstitial cystitis by activating the Wnt/β-catenin signal

Authors: Weilin Fang, Qixiang Song, Tingting Lv, Jianwei Lv, Zhikang Cai, Zhong Wang, Xin Song, Xiang Ji, Jin Huang

Published in: International Urology and Nephrology | Issue 12/2023

Abstract

Background/objective

Serpina3n/Serpina3 has been identified to be implicated in inflammatory diseases, but its role in interstitial cystitis/bladder pain syndrome (IC/BPS) remains unknown. Here, we aimed to reveal serpina3n/serpina3 role in IC/BPS in vivo and in vitro.

Methods

The IC/BPS model in mice was induced by intraperitoneal injection of 150 mg/kg of cyclophosphamide (CYP). HE and toluidine blue staining were used for histology assessment. Serpina3n/serpina3 expression in the bladder tissues from IC/BPS patients and mouse models were determined by qPCR, immunohistochemistry and western blotting. XAV-939 treatment was applied to inhibit β-catenin activation. Serpina3 role in modulating the growth and apoptosis of HBlEpCs, a human primary bladder epithelial cell line, was assessed by CCK-8 and flow cytometry assays.

Results

Serpina3n/serpina3 expression was decreased in both human and mice bladder tissues with IC/BPS. Upregulation of serpina3n significantly alleviated CYP-induced bladder injury, with decreased mast cells and pro-inflammatory factor levels, including IL-1β, IL-6, and TNF-α, while increased IL-10 level. In addition, serpina3 overexpression inhibited the apoptosis of HBlEpCs, and increased cell growth. In mechanism, we found that serpina3 overexpression promoted the activation of wnt/β-catenin signaling. And, the inhibition of wnt/β-catenin signaling with XAV-939 abolished serpina3n/serpina3 role in protecting bladder tissues from CYP-induced cystitis, as well as inhibiting HBlEpC apoptosis.

Conclusion

Serpina3n/serpina3 expression was decreased in IC/BPS. Overexpression of serpina3n could alleviate CYP-induced IC/BPS by activating the Wnt/β-catenin signal. This study may provide a new therapeutic strategy for IC/BPS.

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Title: Serpina3n/serpina3 alleviates cyclophosphamide-induced interstitial cystitis by activating the Wnt/β-catenin signal
Authors: Weilin Fang
Qixiang Song
Tingting Lv
Jianwei Lv
Zhikang Cai
Zhong Wang
Xin Song
Xiang Ji
Jin Huang
Publication date: 18-08-2023
Publisher: Springer Netherlands
Keywords: Cystitis
Cystitis
Published in: International Urology and Nephrology / Issue 12/2023
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI: https://doi.org/10.1007/s11255-023-03726-7

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