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Regulation of Bladder Structure and Function by Micro-RNA29

Micro-RNA29 对膀胱结构和功能的调节

基本信息

批准号：
10397533
负责人：
Dale Edmond Bjorling
金额：
$ 67.06万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-05 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10397533
关键词：
3&apos Untranslated Regions Aging Benign Benign Prostatic Hypertrophy Binding Biopsy Bladder Bladder Diseases Bladder Dysfunction Bladder Tissue Chronic Cicatrix Clinical Trials Collagen Crossbreeding Data Deposition Deterioration Development Disease Elements Enterobacteria phage P1 Cre recombinase Enzymes Extracellular Matrix Extracellular Matrix Proteins Female Fibrosis Functional disorder Genes Genetic Transcription Heart Homeostasis Impairment Inflammation Kidney Knockout Mice Liver Location Lower urinary tract LoxP-flanked allele Lung Mesenchyme Messenger RNA MicroRNAs Mus Neurogenic Bladder Nucleotides Obstruction Oligonucleotides Organ Pathogenesis Patients Play Post-Translational Protein Processing Process Prostatectomy Protein Isoforms Pulmonary Fibrosis RNA Degradation RNA Sequences Radiation therapy Regulation Reporting Research Research Personnel Role Signal Transduction Skin Smooth Muscle Stimulus Structure Testing Therapeutic Time Tissues Translations UPK2 gene Untranslated RNA Urine Urothelium Viral clinical application crosslink effective therapy experimental study human male improved interest interstitial male men novel therapeutic intervention novel therapeutics prevent promoter restoration side effect transcriptome sequencing translational potential vector

项目摘要

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.

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。