Peskar Dominika, Kuret Tadeja, Jeruc Jera, Erman Andreja
Faculty of Medicine, Institute of Cell Biology, University of Ljubljana, 1000 Ljubljana, Slovenia.
Faculty of Medicine, Institute of Pathology, University of Ljubljana, 1000 Ljubljana, Slovenia.
Diagnostics (Basel). 2022 Apr 25;12(5):1078. doi: 10.3390/diagnostics12051078.
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.
间质性膀胱炎/膀胱疼痛综合征(IC/BPS)的病理生理学以及其有效的诊断和治疗方法仍未得到充分了解。研究病理条件下组织糖基化模式的变化是发现新型生物标志物和治疗靶点的一种有前景的方法。IC/BPS的糖生物学在很大程度上尚未得到充分研究,因此我们使用了10种对不同单糖具有偏好的植物凝集素,比较了正常人类膀胱上皮与IC/BPS患者膀胱上皮的糖基化模式。我们还将凝集素与人类膀胱上皮的结合情况与IC/BPS中引用最多的两种实验模型进行了比较,具体而言,即肿瘤坏死因子α(TNFα)处理的人类膀胱上皮细胞系RT4和环磷酰胺诱导的C57BL6/J小鼠慢性膀胱炎。此外,通过荧光显微镜对所选的四种凝集素(刀豆球蛋白A、DSL、红豆凝集素和麦胚凝集素)的结合进行了定性评估,并通过荧光强度(F.I.)测量进行了定量评估。我们的结果显示,红豆凝集素的荧光强度显著降低,以及IC/BPS患者膀胱上皮中麦胚凝集素标记模式发生了显著变化,这表明它们有可能作为IC/BPS组织病理学诊断中有前景的额外生物标志物。我们还表明,所选实验模型与IC/BPS患者之间的膀胱上皮糖基化模式足够相似,可为IC/BPS糖生物学的临床前研究提供一个合适的平台。