Transient receptor potential vanilloid type 4 (TRPV4) in urinary bladder structure and function.
Transient receptor potential vanilloid type 4 (TRPV4) in urinary bladder structure and function.
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DOI：
10.1016/bs.ctm.2022.06.002
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发表时间：
2022
影响因子：
--
通讯作者：
Vizzard, Margaret A
中科院分区：
文献类型：
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作者：
Perkins, Megan Elizabeth;Vizzard, Margaret A
膀胱疼痛综合征（BPS）/间质性膀胱炎（IC）是一种泌尿系统慢性盆腔疼痛综合征，其特征为盆腔疼痛、压迫或伴有泌尿系统症状的不适。症状加重（突发）常见于多种感知触发因素，包括压力。在膀胱中表达的多个瞬时受体电位（TRP）通道（TRPA 1、TRPV 1、TRPV 4）在下尿路（LUT）中具有特定的组织分布，并且涉及膀胱疾病，包括膀胱过度活动症（OAB）和BPS/IC。TRPV 4通道是膀胱中机械传感器的强有力的候选者，TRPV 4拮抗剂是OAB的有前途的治疗剂。在这篇文章中，我们讨论了目前关于LUT中TRPV 4分布和功能的知识，以及它在损伤或疾病中的可塑性，重点是BPS/IC。我们回顾了我们的研究，扩大知识TRPV 4在膀胱功能，重点是（i）TRPV 4参与排尿功能障碍，盆腔疼痛，和非排尿膀胱收缩在NGF-OE小鼠;（ii）扩张诱导的管腔ATP释放机制和（iii）TRPV 4和囊泡释放机制的参与。最后，我们回顾了我们在出生后大鼠中的固有层研究，这些研究表明：（i）TRPV 4+和PDGFRα+固有层细胞网络在出生后早期大鼠中占主导地位;（ii）外源性介质（即，ATP和TRPV 4激动剂）激活和增加表现出活性Ca 2+事件的固有层细胞的数量的能力;和（iii）ATP和TRPV 4激动剂增加对应于偶联的固有层网络事件和传播波前形成的整合Ca 2+活性的速率的能力。
Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a urologic, chronic pelvic pain syndrome characterized by pelvic pain, pressure, or discomfort with urinary symptoms. Symptom exacerbation (flare) is common with multiple, perceived triggers including stress. Multiple transient receptor potential (TRP) channels (TRPA1, TRPV1, TRPV4) expressed in the bladder have specific tissue distributions in the lower urinary tract (LUT) and are implicated in bladder disorders including overactive bladder (OAB) and BPS/IC. TRPV4 channels are strong candidates for mechanosensors in the urinary bladder and TRPV4 antagonists are promising therapeutic agents for OAB. In this perspective piece, we address the current knowledge of TRPV4 distribution and function in the LUT and its plasticity with injury or disease with an emphasis on BPS/IC. We review our studies that extend the knowledge of TRPV4 in urinary bladder function by focusing on (i) TRPV4 involvement in voiding dysfunction, pelvic pain, and non-voiding bladder contractions in NGF-OE mice; (ii) distention-induced luminal ATP release mechanisms and (iii) involvement of TRPV4 and vesicular release mechanisms. Finally, we review our lamina propria studies in postnatal rats studies that demonstrate: (i) the predominance of the TRPV4+ and PDGFRα+ lamina propria cellular network in early postnatal rats; (ii) the ability of exogenous mediators (i.e., ATP, TRPV4 agonist) to activate and increase the number of lamina propria cells exhibiting active Ca2+ events; and (iii) the ability of ATP and TRPV4 agonist to increase the rate of integrated Ca2+ activity corresponding to coupled lamina propria network events and the formation of propagating wavefronts.