Voiding defects in acute radiation cystitis driven by urothelial barrier defect through loss of E-cadherin, ZO-1 and Uroplakin III.
Voiding defects in acute radiation cystitis driven by urothelial barrier defect through loss of E-cadherin, ZO-1 and Uroplakin III.
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DOI：
10.1038/s41598-021-98303-2
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发表时间：
2021-09-29
影响因子：
4.6
通讯作者：
Lamb LE
中科院分区：
文献类型：
--
作者：
Zwaans BMM;Carabulea AL;Bartolone SN;Ward EP;Chancellor MB;Lamb LE
癌症治疗的长期副作用是一个日益增长的医疗保健问题，因为癌症幸存者的预期寿命增加。膀胱损伤在接受盆腔癌放射治疗的患者中很常见，可导致放射性（出血性）膀胱炎（RC）。RC的疾病进展包括急性期和慢性期，中间有一个无复发期。深入了解与这些阶段相关的组织变化对于制定适当的干预措施是必要的。使用小鼠临床前模型，我们先前已经表明，纤维化和血管损伤是慢性RC的主要病理特征。本研究的目的是确定急性RC期间的病理变化。我们发现，放射治疗导致排尿频率暂时增加，照射后4-8周排尿量减少。在组织学上，排尿缺陷与尿路上皮变薄、尿路上皮细胞-细胞粘附和紧密连接蛋白丢失以及尿斑蛋白III表达减少有关。到12周时，尿道再生，排尿模式与同窝对照相似。照射后膀胱组织未见炎症和纤维化。我们的结论是，功能性膀胱缺陷在急性RC驱动主要是由尿路上皮缺损。
Long term-side effects from cancer therapies are a growing health care concern as life expectancy among cancer survivors increases. Damage to the bladder is common in patients treated with radiation therapy for pelvic cancers and can result in radiation (hemorrhagic) cystitis (RC). The disease progression of RC consists of an acute and chronic phase, separated by a symptom-free period. Gaining insight in tissue changes associated with these phases is necessary to develop appropriate interventions. Using a mouse preclinical model, we have previously shown that fibrosis and vascular damage are the predominant pathological features of chronic RC. The goal of this study was to determine the pathological changes during acute RC. We identified that radiation treatment results in a temporary increase in micturition frequency and decrease in void volume 4–8 weeks after irradiation. Histologically, the micturition defect is associated with thinning of the urothelium, loss of urothelial cell–cell adhesion and tight junction proteins and decrease in uroplakin III expression. By 12 weeks, the urothelium had regenerated and micturition patterns were similar to littermate controls. No inflammation or fibrosis were detected in bladder tissues after irradiation. We conclude that functional bladder defects during acute RC are driven primarily by a urothelial defect.
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影响因子：
19.6
作者：
Wu, Xue-Ru;Kong, Xiang-Peng;Pellicer, Angel;Kreibich, Gert;Sun, Tung-Tien
通讯作者：
Sun, Tung-Tien
影响因子：
2.1
作者：
Martin, Sarah E.;Begun, Evan M.;Abdelhady, Mazen
通讯作者：
Abdelhady, Mazen
DOI：
10.1073/pnas.232551499
发表时间：
2002-11-26
影响因子：
11.1
作者：
Neese, RA;Misell, LM;Hellerstein, MK
通讯作者：
Hellerstein, MK
影响因子：
2
作者：
Ikeda, Youko;Zabbarova, Irina V.;Kanai, Anthony J.
通讯作者：
Kanai, Anthony J.
影响因子：
2
作者：
Chuang, Yao-Chi;Tyagi, Pradeep;Chancellor, Michael B.
通讯作者：
Chancellor, Michael B.