Regulation of Bladder Structure and Function by Micro-RNA29

MicroRNA-29(miR-29)已被证明在肺、肝、心脏和皮肤中可以抑制 细胞外基质增多，间质纤维化。初步数据显示纤维化和膀胱功能障碍 在miR-29a/b1整体缺失的小鼠中。关于miR-29a/b1在 维持膀胱内环境稳定或预防或逆转膀胱纤维化及相关膀胱 功能障碍。膀胱壁纤维化增加，并伴随着膀胱功能的恶化 在膀胱出口梗阻、神经原性膀胱疾病患者中观察到放射治疗后， 慢性炎症，并伴随着衰老。在膀胱中观察到miR-29a几乎完全消失。 从接受部分前列腺切除术治疗膀胱出口梗阻的患者获得的组织 良性前列腺增生症与正常男性膀胱组织中miR-29a高表达的比较。 本研究将描述miR-29a对导致膀胱纤维化和膀胱癌的信号转导过程的调制。 小鼠膀胱功能紊乱。这项研究将进一步确定这些变化是否 膀胱中miR-29a/b1特异性丢失的结果以及膀胱功能和膀胱功能的不良变化 修复miR-29a可逆转部分膀胱出口梗阻所致的结构改变。这些 实验具有巨大的转化潜力。各种microRNAs目前正被用于临床 治疗各种疾病的试验。复方丹参胶囊治疗膀胱纤维化及正常膀胱功能丧失 MIR-29代表了一种针对目前缺乏有效治疗的疾病的全新治疗方法 选择。

MicroRNA-29 (miR-29) has been demonstrated in the lung, liver, heart, and skin to inhibit formation of increased extracellular matrix and interstitial fibrosis. Preliminary data indicate fibrosis and bladder dysfunction in mice with global loss of miR-29a/b1. Minimal data are available regarding the role of miR-29a/b1 in maintaining bladder homeostasis or preventing or reversing bladder fibrosis and associated bladder dysfunction. Increased fibrosis of the bladder wall, and concomitant deterioration of bladder function, have been observed in patients with bladder outlet obstruction, neurogenic bladder disorders, after radiation therapy, chronic inflammation, and accompanying aging. Nearly complete loss of miR-29a was observed in bladder tissue obtained from men undergoing partial prostatectomy to treat bladder outlet obstruction associated with benign prostatic hyperplasia compared to abundant miR-29a expression in normal male human bladder tissue. This research will delineate modulation by miR-29a of signaling processes resulting in bladder fibrosis and derangement of bladder function in mice. The research will further determine whether or not these changes are the result of specific loss of miR-29a/b1 in the bladder and whether adverse changes in bladder function and structure induced by partial bladder outlet obstruction can be reversed by restoration of miR-29a. These experiments have significant translational potential. Various microRNAs are currently being used in clinical trials to treat a variety of disorders. Treatment of bladder fibrosis and loss of normal bladder function using miR-29 represents an entirely novel therapeutic approach for disorders that currently lack effective treatment options.