Role of microRNAs in regulation of urothelial permeability

Tight and adherens junctions (TJ, AJ) are indispensable for the barrier function of epithelia and the control of paracellular transport. Bladder urothelium, which forms a lining of the urinary tract, is one of the tightest epithelia of the body. Defects of the urothelial integrity resulting in leakage and activation of underlying sensory nerves are potential causative factors of Bladder Pain Syndrome (BPS), a clinical syndrome of pelvic pain and urinary urgency/frequency in the absence of a specific cause. Previously we have shown that BPS was accompanied by a down-regulation of several TJ proteins, and an up-regulation of microRNAs, including miR-199a-5p. Expression of miR-199a-5p in urothelial and bronchial epithelial cells interferes with the correct intercellular junction formation leading to an aberrant cortical actin distribution and a reduced epithelial tightness. The aim of current project is to identify the mRNAs, targeted by miR-199a-5p, by applying mRNA sequencing methodology and transcriptome analysis to the samples of the human urothelial cells, ectopically expressing this miRNA. Our results will establish a link between the microRNA expression and the control of urothelial permeability. Up-regulation of miR-199a-5p and concomitant down-regulation of its targets during BPS might be detrimental for establishment of tight urothelium barrier, leading to chronic pain.