Interstitial cystitis (IC) is a chronic, aseptic inflammation of the bladder that mainly affects women. The clinical presentation of IC is atypical and often resembles other urinary tract disorders, leading to frequent misdiagnosis. Due to the limited understanding of its etiology and pathophysiology, therapeutic approaches for IC are predominantly symptomatic. Animal models play a crucial role in IC research, and their comprehensive understanding is crucial for translating findings from experimental models to clinical applications.
In the doctoral dissertation, we analyzed the model of IC in C57BL/6J mice of both sexes, induced by repeated low-dose applications of cyclophosphamide, which is one of the most commonly used animal models for IC. A comprehensive analysis of the structural, functional, and sensory properties of this model was performed using a variety of molecular, cell biological, histological, and microscopic techniques.
Our findings indicate that the model effectively reflects key pathological changes observed in the bladder wall of patients with IC, making this model a suitable framework for IC studies. Transcriptome analysis showed that the processes of innate immunity and cell cycle regulation are more enriched in mice with IC compared to control mice. Additionally, differential miRNA expression was observed between control and treated animals, suggesting that some miRNAs could be used as biomarkers for IC. In the bladders of mice with IC, alterations in sensory protein expression and changes in the shape and spatial distribution of interstitial cells in the lamina propria were also observed. Sex-specific responses to IC induction were evident, with females exhibiting more extensive inflammatory changes in the bladder wall and more pronounced urothelial hyperplasia than males. In addition, the restoration of urothelial barrier function after injury was more compromised in treated females than in treated males. This may be related to the less extensive glycosylation of the urothelium in treated females compared to treated males and the different regulation of the actin cytoskeleton between the sexes of the treated animals.
Our research thus confirms the relevance of the mouse IC model for studying this disease and reveals substantial differences in the bladder’s response to chronic inflammation between the sexes. Knowledge of sex-specific disparities, including those revealed in the mouse model in the scope of the doctoral dissertation, may importantly contribute to understanding the mechanisms of IC development and its sex-specific occurrence, as well as to improving diagnostic and therapeutic strategies for IC in the future.
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