Regulation of tight junction proteins and bladder epithelial paracellular permeability by an antiproliferative factor from patients with interstitial cystitis
Regulation of tight junction proteins and bladder epithelial paracellular permeability by an antiproliferative factor from patients with interstitial cystitis
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DOI：
10.1097/01.ju.0000180417.11976.99
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发表时间：
2005-12-01
影响因子：
6.6
通讯作者：
Keay, S
中科院分区：
文献类型：
--
作者：
Zhang, CO;Wang, JY;Keay, S
目的：以前的报道表明，膀胱上皮屏障可能在间质性膀胱炎（IC）中受损。抗增殖因子（anti - prolifative factor， APF）是IC患者膀胱上皮细胞特异性产生的一种小糖蛋白，可诱导某些上皮细胞蛋白的表达改变，并深刻抑制细胞生长。因此，我们证实，与正常对照细胞相比，IC患者活检培养的膀胱上皮细胞单层通透性增加，紧密连接形成减少。然后，我们测定了APF对正常膀胱上皮细胞单层通透性和紧密连接蛋白表达的影响。材料和方法：在Transwell培养板（康宁，康宁，纽约）上，通过测量细胞间的c -14-甘露醇和h -3-菊糖通量来测定渗透性。免疫荧光显微镜观察紧密连接的形成，Western blot检测特异性蛋白的表达。结果：与模拟APF相比，APF处理导致正常膀胱上皮细胞单层的细胞旁通透性显著增加，紧密连接减弱，与IC细胞的变化相似。APF处理也降低了紧密连接蛋白occludens-1和occludin的表达。结论：由于APF对体外膀胱上皮细胞紧密连接和细胞旁通透性的明显影响，APF可能与膀胱上皮屏障渗漏有关。
Purpose: Previous reports have suggested that the bladder epithelial barrier may be compromised in interstitial cystitis (IC). Antiproliferative factor (APF) is a small glycoprotein made specifically by bladder epithelial cells in patients with IC that induces changes in expression of certain epithelial cell proteins and profoundly inhibits cell growth. Therefore, we confirmed the increased permeability and decreased tight junction formation of bladder epithelial cell monolayers grown from biopsies in patients with IC compared to cells from normal controls. We then determined the effect of APF on the permeability of normal bladder epithelial cell monolayers and the expression of tight junction proteins.Materials and Methods: Permeability was determined by measuring the C-14-mannitol and H-3-inulin flux between cells in confluent monolayers on Transwell culture plates (Corning, Corning, New York). Tight junction formation was assessed by immunofluorescence microscopy and the expression of specific proteins was determined by Western blot.Results: APF treatment caused significant increases in the paracellular permeability of normal bladder epithelial cell monolayers and the attenuation of tight junctions compared to mock APF, similar to changes seen in IC cells. APF treatment also decreased expression of the tight junction proteins zonula occludens-1 and occludin.Conclusions: Because of its apparent effects on bladder epithelial cell tight junctions and paracellular permeability in vitro, APF may contribute to the leakiness of the bladder epithelial barrier seen in IC.