Changes of miRNA expression in obstructive and neurogenic bladder dysfunction. bladder dysfunction

Lower urinary tract dysfunction (LUTD) has multiple causes including bladder outlet obstruction (BOO) as a result of benign prostatic hyperplasia (BPH) and neurological diseases including spinal cord injury (SCI). The consequences of both BOO-induced (BLUTD) and neurogenic LUTD (NLUTD), either the low compliance high pressure bladder or the acontractile bladder, are believed to share some pathogenetic mechanisms. Recently we have established miRNA and mRNA expression profiles of several urodynamically defined states of BLUTD. In this follow-up project we propose to extend these studies, undertaking a comparative miRNA and mRNA profiling of BLUTD and NLUTD, and investigate the dynamic alteration of miRNA expression in different functional manifestations of disease. Monitoring the reversal of changes in miRNA expression after relief of obstruction and restoration of normal bladder function will help delineate the key BOO-induced miRNAs with regulatory potential. Similarly, the dynamics of miRNA alteration, observed in SCI patients should reveal the role of miRNA in gene expression regulation during neurogenic-induced organ remodelling. By uncovering the molecular similarities and differences between BLUTD and NLUTD, we will elucidate some of the causative factors in the development of these disorders and highlight the impact of myogenic and neurogenic components postulated to be involved.下尿路功能障碍（Lower urinary tract dysfunction, LUTD）存在多种致病因素，包括由良性前列腺增生（benign prostatic hyperplasia, BPH）引发的膀胱出口梗阻（bladder outlet obstruction, BOO），以及包括脊髓损伤（spinal cord injury, SCI）在内的神经系统疾病。由BOO诱导的下尿路功能障碍（BOO-induced LUTD, BLUTD）与神经源性下尿路功能障碍（neurogenic LUTD, NLUTD），二者均可引发低顺应性高压膀胱或无收缩力膀胱，其发病机制被认为存在共通之处。近期本研究团队已针对数种经尿流动力学明确分型的BLUTD，构建了其微小RNA（microRNA, miRNA）与信使RNA（messenger RNA, mRNA）表达谱。在本后续研究项目中，我们拟拓展前述研究内容，对BLUTD与NLUTD开展对比性miRNA及mRNA表达谱分析，并探究疾病不同功能表型下miRNA表达的动态变化。通过监测解除梗阻、恢复膀胱正常功能后miRNA表达变化的逆转情况，可明确具备调控潜能的关键BOO诱导型miRNA。同理，对脊髓损伤患者中观察到的miRNA改变动态进行研究，可揭示miRNA在神经源性器官重塑过程中对基因表达的调控作用。通过揭示BLUTD与NLUTD之间的分子异同，我们将阐明这类疾病发生发展中的部分致病因素，并阐明推测参与病程的肌源性与神经源性成分所产生的影响。