Zhang Yao, Zhang Jiao, Liu Jiaye, Liang Lang, Zhou Na, Liang Shaochan, Huang Jingyi, Hong Ming, Wang Rui, Xu Siyuan, Gu Chiming, Tan Bo, Cao Hongying
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, No. 232, Waihuan East Road, Guangzhou Higher Education Mega Center, Panyu District, Guangzhou, 510006, Guangdong, China.
The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Traditional Chinese Medicine), Guangzhou, 510006, Guangdong, China.
Mol Med. 2025 Mar 10;31(1):91. doi: 10.1186/s10020-025-01140-6.
Diabetic cystopathy (DCP) is linked to bladder nerve conduction disorders, with diabetes-induced neuropathy impairing nerve signal transmission and causing bladder dysfunction. Myosin 5a, vital for neuronal transport, has been linked to neurological disorders, though its role in DCP remains unclear. The objective of this study was to investigate whether Myosin 5a plays a potential regulatory role in Diabetic Cystopathy.
Bladder strips from diabetic rats were use to assess heightened responsiveness to external stimuli. Urodynamic assessments were conducted to track the progression of bladder voiding dysfunction over time, following streptozotocin (STZ) injection. Single-cell RNA-Seq mining was employed to identify associations between Myosin 5a and bladder overactivity. Cellular and tissue analyses were performed to determine the co-localization of Myosin 5a with neurotransmitter-related proteins. The impact of Myosin 5a knockdown on ChAT and SP expression in bladder neurons was also evaluated. Additionally, Myosin 5a-deficient DBA mice were studied for voiding function and sensitivity to stimuli. Student's t-test (two-tailed) or Mann-Whitney's U test analysis of variance was used to analyze the difference between groups.
Bladder strips from diabetic rats exhibit increased responsiveness to external stimuli, with urodynamic assessments showing a progressive decline in bladder function, culminating in overactivity by the fourth week post-STZ injection. Co-localization of Myosin 5a with neurotransmitter-related proteins was observed, and the knockdown of Myosin 5a in bladder neurons led to a significant reduction in ChAT and SP expression. Myosin 5a-deficient DBA mice exhibited abnormal voiding function and reduced sensitivity to stimuli, along with significant downregulation of SLC17A9. Single-cell RNA-Seq analysis revealed a significant link between Myosin 5a and bladder overactivity, with Myosin 5a expression escalating in tandem with the severity of bladder dysfunction.
Myosin 5a's dysregulation in diabetic rats may worsen bladder overactivity, suggesting its potential as a therapeutic target for diabetic OAB.
糖尿病性膀胱病（DCP）与膀胱神经传导障碍有关，糖尿病引起的神经病变会损害神经信号传递并导致膀胱功能障碍。肌球蛋白5a对神经元运输至关重要，虽已发现其与神经疾病有关，但其在DCP中的作用仍不清楚。本研究的目的是调查肌球蛋白5a是否在糖尿病性膀胱病中发挥潜在的调节作用。
使用糖尿病大鼠的膀胱条来评估对外部刺激的反应性增强。在注射链脲佐菌素（STZ）后，进行尿动力学评估以跟踪膀胱排尿功能障碍随时间的进展。采用单细胞RNA测序挖掘技术来确定肌球蛋白5a与膀胱过度活动之间的关联。进行细胞和组织分析以确定肌球蛋白5a与神经递质相关蛋白的共定位。还评估了肌球蛋白5a敲低对膀胱神经元中ChAT和SP表达的影响。此外，对肌球蛋白5a缺陷的DBA小鼠的排尿功能和对刺激的敏感性进行了研究。使用学生t检验（双侧）或曼-惠特尼U检验方差分析来分析组间差异。
糖尿病大鼠的膀胱条对外部刺激的反应性增加，尿动力学评估显示膀胱功能逐渐下降，在注射STZ后第四周最终导致膀胱过度活动。观察到肌球蛋白5a与神经递质相关蛋白的共定位，并且膀胱神经元中肌球蛋白5a的敲低导致ChAT和SP表达显著降低。肌球蛋白5a缺陷的DBA小鼠表现出异常的排尿功能和对刺激的敏感性降低，同时SLC17A9显著下调。单细胞RNA测序分析揭示了肌球蛋白5a与膀胱过度活动之间的显著联系，肌球蛋白5a的表达随着膀胱功能障碍的严重程度而升高。
糖尿病大鼠中肌球蛋白5a的失调可能会加重膀胱过度活动，表明其作为糖尿病性膀胱过度活动症治疗靶点的潜力。
