Mode of action of sensory transmitters in bladder urothelium and the effect of ageing

膀胱尿道上皮感觉递质的作用模式和衰老的影响

• 批准号: BB/G015554/1
• 负责人: Changhao Wu
• 金额: $ 62.09万
• 依托单位: University of Surrey
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FG015554%2F1
• 关键词: Mode; action; sensory; transmitters; bladder

The role of urothelium, the inner lining of the bladder wall that separates urine from underlying tissues, has recently generated intense interest in the scientific community as a tissue that mediates the sensation of bladder fullness. A significant advance in this area was the demonstration of release of a chemical messenger, ATP, from the urothelium when the bladder is stretched, as occurs during filling, and which eventually activates sensory nerves. The details of this mechanism are unclear, but our previous work identified a hitherto uninvestigated cellular fraction, so-called myofibroblasts, that may have a key role in this sensation. We wish to test the hypothesis that the urothelium, and the associated myofibroblast layer, form a sensory structure in response to bladder filling and harmful stimuli as may accumulate during urinary tract infections, or inflammatory conditions. We will first characterise the responses of these cell structures to physical and chemical stimuli and then investigate the effect of ageing on these processes, using both animal models and human samples. The project will provide novel insights into sensory function of hollow organs and processes of ageing; it will also identify molecular targets from which drugs may be developed to control bladder activity when it becomes dysfunctional.

尿路上皮是膀胱壁的内层，它将尿液与底层组织分离开来，作为一种调节膀胱充溢感的组织，它的作用最近引起了科学界的强烈兴趣。这一领域的一个重大进展是，当膀胱被拉伸时，尿路上皮会释放一种化学信使ATP，就像在充盈过程中发生的那样，并最终激活感觉神经。这种机制的细节尚不清楚，但我们之前的工作发现了一种迄今未被研究的细胞部分，即所谓的肌成纤维细胞，它可能在这种感觉中起关键作用。我们希望验证尿路上皮和相关的肌成纤维细胞层在膀胱充盈和有害刺激时形成感觉结构的假设，这些刺激可能在尿路感染或炎症条件下积累。我们将首先描述这些细胞结构对物理和化学刺激的反应，然后研究衰老对这些过程的影响，使用动物模型和人类样本。该项目将为中空器官的感觉功能和衰老过程提供新的见解；它还将确定分子靶点，从而开发出药物来控制膀胱功能失调时的活动。

项目成果

Effect of carvedilol on cardiomyocyte apoptosis in a rat model of myocardial infarction: a role for toll-like receptor 4.

• DOI: 10.4103/0253-7613.117729
• 发表时间: 2013-09
• 期刊: Indian journal of pharmacology
• 影响因子: 2.4
• 作者: Liu Q;Zhang J;Xu Y;Huang Y;Wu C
• 通讯作者: Wu C

Angiotensin II as a novel regulator of urothelial and bladder function Physiological society annual meeting 2014 30th June 2 July London C71 , abstract 95P.

血管紧张素 II 作为尿路上皮和膀胱功能的新型调节剂生理学会年会 2014 年 6 月 30 日 7 月 2 日伦敦 C71，摘要 95P。

• 发表时间: 2014
• 作者: L. Adjei

The functional role of acid-sensing channel 3 in the urinary bladder

膀胱酸敏感通道3的功能作用

• 发表时间: 2013
• 期刊: 37th Congress of IUPS (2013) Proceedings
• 作者: Adjei, L.

Identification of NADPH oxidases and oxidative stress in the bladder

膀胱中 NADPH 氧化酶和氧化应激的鉴定

• 发表时间: 2015
• 作者: Adjei L

Enhanced autophagic flux by endoplasmic reticulum stress in human hepatocellular carcinoma cells contributes to the maintenance of cell viability.

• DOI: 10.3892/or.2013.2474
• 发表时间: 2013-07
• 期刊: Oncology reports
• 影响因子: 4.2
• 作者: Tai Ma;Yuan-yuan Li;Jie Zhu;Lu-lu Fan;Wei-Dong Du;Chang-hao Wu;G. Sun;Jia-bin Li