Increased Cell Apoptosis of Urothelium Mediated by Inflammation in Interstitial Cystitis/Painful Bladder Syndrome
Increased Cell Apoptosis of Urothelium Mediated by Inflammation in Interstitial Cystitis/Painful Bladder Syndrome
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DOI：
10.1016/j.urology.2011.09.049
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发表时间：
2012-02-01
期刊：
影响因子：
2.1
通讯作者：
Kuo, Hann-Chorng
中科院分区：
文献类型：
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作者：
Shie, Jia-Heng;Liu, Hsin-Tzu;Kuo, Hann-Chorng
目的探讨间质性膀胱炎/膀胱疼痛综合征（IC/PBS）中膀胱炎症是否可以直接调节尿路上皮细胞凋亡增加的信号通路。慢性炎症和尿路上皮稳态受损可能是IC/PBS的发病机制。方法共有29例IC/PBS患者和5例对照患者纳入本研究。采用双染、蛋白芯片分析和蛋白质印迹分析 IC/PBS 患者和对照患者膀胱粘膜标本中 caspase 3、Bad、Bax、磷酸化 p53、磷酸化 p38 α 和肿瘤坏死因子 α (TNF-α) 的变化。使用 ImageJ 处理对阵列和蛋白质印迹中蛋白质的强度进行定量。使用末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸切口末端标记染色和蛋白质印迹分析炎症分子处理的尿路上皮细胞中参与凋亡的分子水平。 结果 Phospho-p38 和末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸切口末端标记双重染色 表明炎症和细胞凋亡事件在 IC/PBS 膀胱中共存。蛋白质-抗体阵列分析显示 IC/PBS 样品中多种炎症分子增加。我们还发现 IC/PBS 膀胱中促凋亡蛋白的水平显着增加，包括磷酸化 p53 (Ser 15)、Bad、Bax 和裂解的 caspase-3。这些结果通过免疫印迹得到证实，并表明 IC/PBS 膀胱中的组织损伤和异常尿路上皮可能同时受到炎症信号的调节，例如 p38 丝裂原激活蛋白激酶和 TNF-α。体外分析还表明，TNF-α治疗和茴香霉素刺激可诱导正常尿路上皮细胞发生凋亡过程。 结论 IC/PBS患者尿路上皮细胞凋亡可能是由于炎症信号上调所致，包括p38丝裂原激活蛋白激酶和TNF-α。泌尿学 79: 484.e7-484.e13, 2012。(c) 2012 年由爱思唯尔公司出版。
OBJECTIVE To investigate whether bladder inflammation could directly modulate the signaling pathway of increased urothelial cell apoptosis in interstitial cystitis/painful bladder syndrome (IC/PBS). Chronic inflammation and impaired urothelial homeostasis are possible pathogenesis of IC/PBS.METHODS A total of 29 patients with IC/PBS and 5 control patients were enrolled in the present study. Double stain, protein array analysis, and Western blotting were performed to analyze the alterations of caspase 3, Bad, Bax, phospho-p53, phospho-p38 alpha, and tumor necrosis factor-alpha (TNF-alpha) in bladder mucosa specimens from patients with IC/PBS and control patients. The intensities of the proteins in the arrays and Western blots were quantified using ImageJ processing. Inflammatory molecule-treated urothelial cells were analyzed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining and Western blotting for the level of molecules involved in apoptosis.RESULTS Phospho-p38 and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling double staining indicated that inflammatory and apoptotic events coexisted in the IC/PBS bladder. Protein-antibody array analysis showed that several inflammatory molecules were increased in the IC/PBS samples. We also found that the levels of pro-apoptotic proteins, including phospho-p53 (Ser 15), Bad, Bax, and cleaved caspase-3 were significantly increased in the IC/PBS bladders. These results were confirmed by immunoblotting and suggested that the tissue damage and abnormal urothelium in the IC/PBS bladder might be regulated concurrently by inflammatory signals, such as p38 mitogen-activated protein kinase and TNF-alpha. The in vitro analysis also showed that the apoptotic process could be induced by TNF-alpha treatment and anisomycin stimulation in normal urothelial cells.CONCLUSION Apoptosis of urothelial cells in patients with IC/PBS could result from upregulation of inflammatory signals, including p38 mitogen-activated protein kinase and TNF-alpha. UROLOGY 79: 484.e7-484.e13, 2012. (c) 2012 Published by Elsevier Inc.