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.
The purpose of this research is to determine the capacity of microRNA-29a to limit fibrosis and loss of normal bladder function. Treatment of patients with microRNA-29a represents a new therapeutic alternative to reverse bladder scarring and restore normal bladder function in patients with bladder fibrosis resulting from bladder outlet obstruction, neurogenic bladder disorders, radiation therapy, chronic inflammation, or aging.
