复发性和持续性尿路感染患者尿路上皮细胞增殖、细胞骨架和屏障功能蛋白表达的缺陷。

Deficits of urothelial cell proliferation, cytoskeleton, and barrier function protein expressions in patients with recurrent and persistent urinary tract infections.

机构信息

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan.

Department of Laboratory Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.

出版信息

Low Urin Tract Symptoms. 2021 Apr;13(2):203-209. doi: 10.1111/luts.12351. Epub 2020 Nov 1.

Abstract

OBJECTIVES

Recurrent urinary tract infection (rUTI) is a common infectious disease in women. This study investigated the urothelial cell proliferation, the cytoskeleton, barrier proteins, and inflammatory protein expression in women with rUTIs.

METHODS

Female patients with recurrent or persistent UTIs were recruited. Bladder mucosal specimens were investigated by Western blot and immunohistochemical staining for the urothelial cytoskeleton proteins cytokeratin 5 (CK5), CK14, and CK20; proteins involved in cellular proliferation, including CD34, sonic hedgehog (SHH), and tumor protein 63 (TP63); barrier proteins zonula occludens 1 (ZO-1) and E-cadherin; inflammatory proteins p38 and tryptase; and proapoptotic proteins Bcl2-associated agonist of cell death protein (BAD), Bcl2-associated X protein (BAX), and caspase-3. Women with stress urinary incontinence without bladder symptoms served as controls. Bladder specimens from 18 recurrent UTI patients with rUTIs and 12 persistent UTIs, and 17 controls were analyzed, and protein expressions were compared between the three groups.

RESULTS

Cell proliferation protein expression for CD34, SHH, and TP63 was significantly lower in the urothelium of patients with rUTIs than in controls. Expression of CK5 increased, whereas CK20 decreased significantly in rUTIs compared with those of controls. Apoptotic proteins BAD, BAX, and caspase-3 were significantly higher in patients with rUTIs. However, barrier proteins ZO-1 and E-cadherin, and tryptase were not significantly lower in patients with rUTIs.

CONCLUSION

Deficits in expression of proteins involved in urothelial cell proliferation, cytoskeleton, and barrier function were noted in patients with rUTIs. These urothelial deficits may be due to deficient proliferation and differentiation resulting in inadequate urothelial barrier function and further in rUTIs.

摘要

目的

复发性尿路感染(rUTI)是女性常见的传染病。本研究调查了患有 rUTI 的女性的尿路上皮细胞增殖、细胞骨架、屏障蛋白和炎症蛋白表达。

方法

招募患有复发性或持续性尿路感染的女性患者。通过 Western blot 和免疫组织化学染色研究膀胱黏膜标本中细胞角蛋白 5(CK5)、CK14 和 CK20 等尿路上皮细胞骨架蛋白;细胞增殖相关蛋白包括 CD34、 sonic hedgehog(SHH)和肿瘤蛋白 63(TP63);屏障蛋白包括紧密连接蛋白 1(ZO-1)和 E-钙黏蛋白;炎症蛋白 p38 和类胰蛋白酶;以及促凋亡蛋白 Bcl2 相关的细胞死亡蛋白激活剂(BAD)、Bcl2 相关 X 蛋白(BAX)和半胱氨酸蛋白酶 3。以无膀胱症状的压力性尿失禁女性作为对照。分析了 18 例复发性 UTI 伴 rUTI 患者和 12 例持续性 UTI 患者及 17 例对照的膀胱标本,比较三组之间的蛋白表达。

结果

rUTI 患者的尿路上皮细胞增殖蛋白 CD34、SHH 和 TP63 的表达明显低于对照组。rUTI 患者的 CK5 表达增加,而 CK20 表达明显低于对照组。rUTI 患者的凋亡蛋白 BAD、BAX 和半胱氨酸蛋白酶 3 明显升高。然而,rUTI 患者的 ZO-1 和 E-钙黏蛋白及类胰蛋白酶的表达并无明显降低。

结论

rUTI 患者的尿路上皮细胞增殖、细胞骨架和屏障功能相关蛋白表达不足。这些尿路上皮缺陷可能是由于增殖和分化不足导致的尿路上皮屏障功能不足,进而导致 rUTI。

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