Presentation Authors: Sarah N. Bartolone*, Elijah P. Ward, Michael B. Chancellor, Kenneth M. Peters, Laura E. Lamb, Royal Oak, MI
Introduction: Hunner's lesions in a subset of interstitial cystitis/bladder pain syndrome (IC/BPS) patients who are difficult to diagnose and treat. There is little understanding on how Hunner's lesions are distinct from the rest of the bladder other than appearance. In this pilot study, tissue biopsies of Hunner's lesions were compared to adjacent, non-lesion areas of the bladder in the same patient to determine if there were differences in protein expression.
Methods: Two bladder biopsies were collected from IC/BPS patients with Hunner's lesions (N=4)- one from area of distinct Hunner's lesion and the other from adjacent, non-lesion areas of the bladder. Protein expression of the bladder samples were profiled using highly sensitive nano Liquid Chromatography with tandem mass spectrometry. Proteins with a p-value less than 0.05 and a fold change greater than 4 were examined for further analysis. Protein-protein interactions were predicted using STRING pathway analysis.
Results: Between areas with Hunner's lesions and those without, proteomic analysis of revealed significant differences in 28 proteins. Analysis of proteins interactions suggests there is a decrease in proteins association with ubiquitination, which is usually involved in protein degradation. Exportin-1, which regulates nuclear export of proteins and RNAs, was also significantly decreased in Hunner's lesions compared to adjacent tissue.
Conclusions: Here we demonstrate through the direct analysis of bladder tissues in the same patient that areas of the bladder with Hunner's lesions are distinct from adjacent, non- lesion tissue on a proteomic level. Ubiquitination and cytosolic protein export signaling network were perturbed in areas with Hunner's lesions. Ubiquitination usually serves as a signal for protein degradation via the proteasome and its misregulation has been demonstrated to have severe impacts in other diseases. Validation of this pilot study may help understand the pathology of IC/BPS with and without Hunner's lesion and open new avenues of novel therapeutic targets.
Source of Funding: We would like to thank Beaumont Urology and the Taubman family for their generous support of interstitial cystitis research including this project.