Changes of microRNA Expression in Obstructive and Neurogenic Bladder Dysfunction Reveal Common Signalling Pathways Relevant for Disease Progression and Recovery

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). Manifestations of LUTD include storage symptoms such as increased daytime frequency, nocturia, urgency and urinary incontinence and voiding symptoms such as slow stream, hesitancy and incomplete emptying. The consequences of both BOO-induced (BLUTD) and neurogenic LUTD (NLUTD), leading to functional entities including the low compliance high pressure bladder as well as the acontractile high volume low pressure bladder, are believed to share some pathogenetic mechanisms.

In a previous project, the investigators have established micro ribonucleic acid (miRNA) and messenger ribonucleic acid (mRNA) expression profiles of several urodynamically defined states of BLUTD. In this follow-up project, the investigators propose to extend these studies, undertaking a comparative miRNA and RNA profiling of BLUTD and NLUTD, and investigate the dynamic alteration of microRNA expression in different functional manifestations of disease. The investigators propose to validate primary gene targets of miRNAs differentially expressed in urodynamically defined states of BLUTD and identify signaling pathways, activated during the progression from hypertrophy to decompensation. 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 during the development and management of NLUTD 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, the investigators 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. The project involves close collaboration between clinical and basic research, and combines the analysis of human biopsy material with in vitro cell-based assays, creating a comprehensive platform for the dissection of molecular mechanisms of LUTD. This project will keep the momentum of the investigators' previous research and contribute to the basic and applied studies into bladder remodeling. It is a logical continuation of their on-going studies of the role of miRNAs in LUT disorders but represents a novel direction of research and has high diagnostic and therapeutic potential.