ArticleInternational urogynecology journal2025
A2A Adenosine Receptor as a Potential Therapeutic Target in Cystitis-Induced Bladder Pain: Insights from a Transgenic Autoimmune Cystitis Murine Model.
Article in International urogynecology journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeBladder pain syndrome (BPS) is associated with heightened inflammatory responses. We hypothesize that reduced A2A adenosine receptor (A2AR) expression exacerbates inflammation and pain, while A2AR activation mitigates these effects. In this study, we aimed to investigate the therapeutic potential of A2AR modulation in an autoimmune cystitis model.
methodsURO-OVA mice, a transgenic model that expresses ovalbumin (OVA) in the bladder urothelium leading to autoimmune-driven cystitis, were randomly divided into four groups (n = 6 per group): (1) control, (2) inflammation-induced (cystitis), (3) inflammation-induced treated with the A2AR agonist regadenoson (a selective A2AR agonist commonly used in cardiac stress tests), and (4) inflammation-induced treated with the A2AR antagonist ZM241385. Bladder inflammation was assessed via histological analysis, western blot, and RT-PCR of inflammatory markers (IL-6, TNF-α, CD11b, GFAP, HMGB1). Bladder pain was measured using bladder distention-evoked visceromotor responses (VMR) and von Frey filament-based pelvic nociception tests.
resultsInflammation-induced mice showed significantly reduced A2AR expression (~50% lower vs. controls, p < 0.001), while other inhibitory factors (e.g., IL-10R, TGF-βR, PD-1) remained largely unchanged. Regadenoson treatment reduced IL-6 and TNF-α expression by ~60% compared to cystitis-induced mice and alleviated pain, whereas ZM241385 worsened inflammation and increased pain responses.
conclusionA2AR downregulation correlates with increased inflammation in the URO-OVA model of BPS. Activation of A2AR via regadenoson significantly suppresses inflammatory responses and bladder pain, suggesting A2AR is a promising therapeutic target for BPS.
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