The role of miRNAs in bladder contractility

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs which modulate gene expression. Biogenesis of miRNAs depends on the activity of the endonucleases Dicer and Drosha. miRNAs are important for processes ranging from development to tumorigenesis. miRNAs also play an important role in vascular smooth muscle differentiation, in part through effects of miR‐145. The role of miRNAs in urinary bladder structure and function still remains unexplored, however. Here we investigated the role of miRNAs in the urinary bladder using conditional smooth muscle‐specific Dicer‐deficient mice. Ultrastructure was examined by electron microscopy (EM) and contractility by myography. Detrusor nerves were activated using electrical field stimulation. Differentiation was assessed by measuring the content of contractile proteins by immunoblotting. The Dicer KO detrusor displayed a substantial decrease in force in response to carbachol and high K+. Stress was however unchanged suggesting reduced bladder wall thickness. No reduction in the relative expression of contractile proteins could be observed. No conspicuous ultrastructural differences were observed by EM but cellular distances appeared increased. Smooth muscle miRNAs are thus essential for detrusor function independently of an effect on smooth muscle differentiation markers. Supported by Swedish Research Council, Faculty of Medicine at Lund University.