Bladder overactivity involves overexpression of MicroRNA 132 and nerve growth factor.

aimHere, we assessed the expression of non-protein coding microRNAs (miRs), nerve growth factor and inflammatory molecules in the rat model of acetic acid induced bladder overactivity. MAIN

methodsUnder isoflurane anesthesia, adult female Sprague-Dawley rats were instilled for 30min with either saline or NGF antisense oligonucleotide complexed with liposomes. 24h later, treated rats were exposed to either intravesical infusion of saline or saline containing 0.25% acetic acid at the rate of 0.04mL/min for 2h under urethane anesthesia (1g/kg; s.c). After CMG, bladder was harvested to study expression of NGF, cytokines and 8 specific miRNAs involved in bladder dysfunctions. The role of miR-132 in bladder overactivity was independently assessed through bladder wall transfection of plasmid encoding miR-132. KEY

findingsNGF overexpression in bladder overactivity was associated with ~2-fold upregulation and downregulation of miR-132 and miR-221, respectively. Pretreatment with NGF antisense restored the expression of miR-221 and miR-132 to control levels and also reduced the expression of NGF and cytokines (MCP-1 and sICAM-1). There was insignificant alteration in the expression of miR-199a-5p, and expression of, miR-210, miR-212, miR-155, miR-134 and miR-206 remained similar across the experimental groups. Bladder wall transfection of miR-132 plasmid in absence of acetic acid exposure was able to independently induce bladder overactivity, bladder hypertrophy and upregulate the expression of NGF and other cytokines. SIGNIFICANCE: Overall, our work sheds light on the role of miR-132 in bladder overactivity, bladder hypertrophy, NGF signaling and expression of inflammatory mediators. Findings demonstrate that aberrant expression of NGF and miR-132 is involved in voiding dysfunctions.