Transcriptomic Characterization of the Porcine Urinary Bladder Trigone Following Intravesical Administration of Resiniferatoxin: Insights from High-Throughput Sequencing.

Abstract

Resiniferatoxin (RTX), a potent capsaicin analog, is being investigated as a therapeutic agent for neurogenic conditions, particularly those affecting bladder control. However, the transcriptomic effects of RTX on the urinary bladder remain largely unexplored. This study aimed to characterize the transcriptomic changes in the porcine urinary bladder trigone region removed seven days post-treatment with intravesical RTX administration (500 nmol per animal in 60 mL of 5% aqueous solution of ethyl alcohol). High-throughput sequencing identified 126 differentially expressed genes (DEGs; 66 downregulated, 60 upregulated), 5 differentially expressed long non-coding RNAs (DELs), and 22 other RNAs, collectively involved in 175 gene ontology (GO) processes. Additionally, differential alternative splicing events (DASes) and single nucleotide variants (SNVs) were detected. RTX significantly modulated signaling pathways related to nerve growth and myelination. Changes in genes associated with synaptic plasticity and neuromodulation were observed, particularly within serotoninergic and cholinergic signaling. RTX altered the expression of immune-related genes, particularly those involved in chemokine signaling and immune regulation. Notably, altered gene expression patterns suggest a potential anti-cancer role for RTX. These findings provide new insights into RTX's therapeutic effects beyond TRPV1 receptor interactions, filling a critical gap in our understanding of its molecular impact on bladder tissue.