Abnormalities in Expression of Structural, Barrier and Differentiation Related Proteins, and Chondroitin Sulfate in Feline and Human Interstitial Cystitis.

Abnormalities in Expression of Structural, Barrier and Differentiation Related Proteins, and Chondroitin Sulfate in Feline and Human Interstitial Cystitis.
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DOI:
10.1016/j.juro.2015.01.090
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发表时间:
2015-08
期刊:
The Journal of urology
影响因子:
--
通讯作者:
Hurst RE
Hurst RE
中科院分区:
其他
文献类型:
--
作者:
Hauser PJ;VanGordon SB;Seavey J;Sofinowski TM;Ramadan M;Abdullah S;Buffington CA;Hurst RE

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对诊断为猫间质性膀胱炎(FIC)的猫的尿道进行分析,以确定是否可以检测到蛋白质表达模式的异常,以及表达模式是否与在人类间质性膀胱炎/膀胱疼痛综合征(IC)患者中观察到的相似。所分析的蛋白质参与细胞粘附、屏障功能,包括糖胺聚糖(GAG)层,或者是分化标志物。福尔马林固定的活组织检查,从8只猫与FIC和7个健康对照标记使用免疫组化和评分使用修改版本的系统以前用于人类样本。进行聚类分析,以调查标记和样品之间的关系。结果显示,89%的FIC膀胱显示异常的蛋白质表达和硫酸软骨素(CS)模式,而只有27%的正常组织表现出轻微的异常。FIC中大部分表达缺失,双糖链(87.5%)、CS(100%)、核心蛋白聚糖(100%)、E-钙粘蛋白(100%)、角蛋白-20(K20)(100%)、尿斑蛋白(50%)、ZO-1(87.5%)。在FIC膀胱中,约75%的CS、双糖链蛋白聚糖和核心蛋白聚糖样品显示不存在管腔染色或无染色。聚类分析的结果显示,FIC和正常样本分为两个明显不同的组,表明FIC猫的尿道扩张与正常相比发生了改变。FIC在管腔GAG和几种蛋白质中产生与在人类患者中观察到的相似的变化,这表明机制中存在一些共性,并支持使用FIC作为人类IC的模型。
The urothelium of cats diagnosed with feline interstitial cystitis (FIC) was analyzed to determine if abnormalities in protein expression patterns could be detected, and whether the pattern of expression was similar to that observed in human Interstitial Cystitis/Bladder Pain Syndrome (IC) patients. The proteins that were analyzed are involved in cell adhesion, barrier function, comprise the glycosaminoglycan (GAG) layer, or are markers of differentiation. Formalin-fixed biopsies from 8 cats with FIC and 7 healthy controls were labeled using immunohistochemistry and scored using a modified version of a system previously used for human samples. Cluster analysis was performed to investigate relationships between the markers and samples. The results showed that 89% of the FIC bladders displayed abnormal protein expression and chondroitin sulfate (CS) patterns, whereas only 27% of the normal tissues exhibited slight abnormalities. Abnormalities were found in most of the FIC samples, biglycan (87.5%), CS (100%), decorin (100%), E-cadherin (100%), keratin-20 (K20, 100%), uroplakin (50%), ZO-1 (87.5%). In the FIC bladders, about 75% of the CS, biglycan, and decorin samples displayed absence of luminal staining or no staining. Results from the cluster analysis revealed that the FIC and normal samples fell into two clearly separate groups, demonstrating that the urothelium of cats with FIC is altered from normal. FIC produces similar changes in luminal GAG and several proteins as is seen in human patients, suggesting some commonality in mechanism and supporting the use of FIC as a model for human IC.