Lectins as Biomarkers of IC/BPS Disease: A Comparative Study of Glycosylation Patterns in Human Pathologic Urothelium and IC/BPS Experimental Models

凝集素作为 IC/BPS 疾病的生物标志物:人类病理尿路上皮和 IC/BPS 实验模型中糖基化模式的比较研究

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作者:Dominika Peskar, Tadeja Kuret, Jera Jeruc, Andreja Erman

Abstract

Pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) remains poorly understood, as well as its effective diagnosis and therapy. Studying changes in tissue glycosylation patterns under pathological conditions is a promising way of discovering novel biomarkers and therapeutic targets. The glycobiology of IC/BPS is largely understudied, therefore we compared glycosylation patterns of normal human urothelium with the urothelium of IC/BPS patients using a selection of 10 plant-based lectins with different monosaccharide preferences. We also compared lectin binding to human urothelium with the two most cited experimental models of IC/BPS, specifically, TNFα-treated human urothelial cell line RT4 and cyclophosphamide-induced chronic cystitis in C57BL6/J mice. Furthermore, binding of four of the selected lectins (ConA, DSL, Jacalin and WGA) was evaluated qualitatively by means of fluorescence microscopy, and quantitatively by fluorescence intensity (F.I.) measurements. Our results reveal a significant reduction in F.I. of Jacalin, as well as a prominent change in the WGA labeling pattern in the urothelium of IC/BPS patients, suggesting their potential use as promising additional biomarkers for histopathological diagnosis of IC/BPS. We have also shown that urothelial glycosylation patterns between selected experimental models and patients with IC/BPS are similar enough to offer an adequate platform for preclinical study of IC/BPS glycobiology.

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