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

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.