Upregulated Expression of TRPV1 and TRPV4 in the Urethra Following Cyclophosphamide-Induced Cystitis in Rats: A Potential Mechanism of Bladder-Urethral Dysfunction.
Yeonwoo Jeong, Seong Hyeon Yu, Ho Seok Chung, Do Gyeong Lim, Sun-Ouck Kim
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Abstract
Purpose: This study aimed to investigate the impact of cyclophosphamide (CYP)-induced cystitis on the expression of transient receptor potential vanilloid 1 (TRPV1) and 4 (TRPV4) in the rat urethra, and to evaluate their potential roles in urethral contribution to bladder dysfunction during inflammation.
Methods: Female rats were divided into the control and CYP-treated groups to induce cystitis. After 72 hours, cystometric analysis was performed to evaluate voiding changes, and urethral TRPV1 and TRPV4 expression was assessed by Western blot and immunofluorescence.
Results: Cystitis rats exhibited a significantly shorter contraction interval (5.9±1.2 minutes vs. 14.7±0.8 minutes, P<0.05) and higher contraction pressure (16.3±0.9 mmHg vs. 10.1±1.3 mmHg, P<0.05) compared to controls. TRPV1 expression was predominant in the urethral mucosal cytoplasm and smooth muscle cells, whereas TRPV4 was largely localized to the cell membranes and perimuscular connective tissues. Both TRPV1 and TRPV4 protein levels were significantly upregulated in the cystitis group (P<0.05).
Conclusion: The upregulation and differential localization of TRPV1 and TRPV4 in the urethra during cystitis suggest their involvement in the pathophysiological mechanisms underlying inflammation-induced lower urinary tract dysfunction. These channels may mediate altered sensory or contractile signaling in the urethra in response to bladder inflammation.
目的：本研究旨在探讨环磷酰胺（CYP）诱导的膀胱炎对大鼠尿道中瞬时受体电位香兰素1 （TRPV1）和TRPV4 （TRPV4）表达的影响，并探讨其在炎症期尿道对膀胱功能障碍的潜在作用。方法：将雌性大鼠分为对照组和cyp治疗组诱导膀胱炎。72h后进行尿量分析评估排尿变化，并采用Western blot和免疫荧光法检测尿道TRPV1和TRPV4的表达。结果：膀胱炎大鼠收缩间隔明显缩短（5.9±1.2 min vs. 14.7±0.8 min）。结论：膀胱炎时尿道TRPV1和TRPV4的上调和差异定位提示其参与炎症性下尿路功能障碍的病理生理机制。这些通道可能在膀胱炎症反应中介导尿道感觉或收缩信号的改变。
期刊介绍：
The International Neurourology Journal (Int Neurourol J, INJ) is a quarterly international journal that publishes high-quality research papers that provide the most significant and promising achievements in the fields of clinical neurourology and fundamental science. Specifically, fundamental science includes the most influential research papers from all fields of science and technology, revolutionizing what physicians and researchers practicing the art of neurourology worldwide know. Thus, we welcome valuable basic research articles to introduce cutting-edge translational research of fundamental sciences to clinical neurourology. In the editorials, urologists will present their perspectives on these articles. The original mission statement of the INJ was published on October 12, 1997.
INJ provides authors a fast review of their work and makes a decision in an average of three to four weeks of receiving submissions. If accepted, articles are posted online in fully citable form. Supplementary issues will be published interim to quarterlies, as necessary, to fully allow berth to accept and publish relevant articles.
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