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Beta-3 adrenergic receptors could be significant factors for overactive bladder-related symptoms
Fukashi Yamamichi1, Katsumi Shigemura2, Hosny M Behnsawy3
1Department of Organs Therapeutics, Division of Urology, Faculty of Medicine, Kobe University Graduate School of Medicine 7-5-1 Kusunoki-Cho, Chuo-Ku, Kobe 650-0017, Japan ; Department of Urology, Hyogo Prefectural Amagasaki General Medical Center 2-17-77 Higashi Naniwa-cho, Amagasaki 660-8550, Japan.
Abstract:
The treatment failure often happens in overactive bladder (OAB) partly owing to its unknown pathogenesis. The purpose of this study is to find significant receptors or biological markers for OAB-related symptoms for establishment of potential order-made therapeutic strategies. The overactive bladder symptom scores (OABSS) and international prostate symptom scores (IPSS)/quality of life (QOL) were questioned in all the 18 patients with OAB diagnosis. Their bladder mucosal tissues were taken from the random biopsy of bladder cancer suspected patients without any finding such as inflammation or carcinoma in situ. They were investigated quantitatively by immunohistochemical (IHC) stainings for inflammatory or immune-system (Interleukin (IL)-6 and cyclooxygenase-2 (Cox-2)), Caspase-3 apoptosis markers, angiogenesis (CD-31), epithelial-mesenchymal transition (E-cadherin) and muscarinic receptor (Muscarine-2 (M)-2), adrenergic receptors (ARs) (alpha 1-d (α1-d) and beta-3 (β-3)). The statistical correlation between the expressions of these 5 markers and 3 receptors and these symptom scores were examined under the comparison between OAB patients and control patients who had urgency score with less than 2 in OABSS. The OABSS and IPSS/QOL was 7.39 ± 2.69 and 21.2 ± 6.59/4.33 ± 1.33, respectively but those of control patients were 2.00 ± 1.41 and 10.1 ± 9.52/2.14 ± 1.46, respectively (P<0.05). Regarding the correlation of those markers' expressions and symptom scores, in OAB patients, OABSS total significantly correlated with β-3 AR expressions (P=0.0457). IPSS post-voiding significantly correlated with β-3 AR expressions (P=0.0308) but no significant relationship in control patients (P>0.05). In conclusion, this study demonstrated that β-3 AR in our tested 8 markers or receptors was correlated strongly with OAB-related symptoms. These data may help elucidate the pathophysiology of OAB and offer possible strategy for its order-made therapies.
Insights
Overactive bladder (OAB) treatment failure may stem from unknown causes. This study found that beta-3 adrenergic receptors (β-3 AR) strongly correlate with OAB symptoms, suggesting a target for personalized therapies.
Area of Science:
- Urology
- Molecular Biology
- Pharmacology
Background:
- Treatment failure in overactive bladder (OAB) is common, often due to poorly understood pathogenesis.
- Identifying specific biological markers is crucial for developing targeted therapeutic strategies for OAB.
Purpose of the Study:
- To investigate potential biological markers and receptors associated with overactive bladder symptoms.
- To explore correlations between marker/receptor expression and symptom severity for personalized OAB treatment.
Main Methods:
- Quantitative immunohistochemical staining of bladder mucosal tissues from OAB patients and controls.
- Analysis of inflammatory markers (IL-6, Cox-2), apoptosis marker (Caspase-3), angiogenesis marker (CD-31), EMT marker (E-cadherin), and receptors (M-2, α1-d AR, β-3 AR).
- Statistical correlation analysis between marker/receptor expression and Overactive Bladder Symptom Scores (OABSS) and International Prostate Symptom Scores (IPSS)/Quality of Life (QOL).
Main Results:
- OAB patients exhibited significantly higher OABSS and IPSS/QOL scores compared to controls (P<0.05).
- A significant correlation was found between total OABSS and beta-3 adrenergic receptor (β-3 AR) expression in OAB patients (P=0.0457).
- Post-voiding IPSS also significantly correlated with β-3 AR expression in OAB patients (P=0.0308).
Conclusions:
- Beta-3 adrenergic receptors (β-3 AR) show a strong correlation with overactive bladder symptoms.
- These findings may contribute to understanding OAB pathophysiology.
- The results suggest β-3 AR as a potential target for developing personalized OAB therapies.
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