Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Urology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
Department of Molecular Parasitology and Tropical Diseases, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Center for International Tropical Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
J Microbiol Immunol Infect. 2021 Apr;54(2):193-205. doi: 10.1016/j.jmii.2019.05.008. Epub 2019 Jun 19.
Patients with diabetes mellitus (DM) have higher incidence and more severe urinary tract infections (UTIs) for longer duration than those of the patients without DM. It causes more complicated etiologies during uropathogenic Escherichia coli (UPEC) infection. However, studies regarding the molecular mechanism are scarce.
The present study (1) aimed to verify if sugar influences the process of UPEC-induced cystitis and invasion into the uroepithelial cells and (2) illustrated the mechanism of effects for sugar enhanced the UPEC infection into uroepithelial cells is related to TLR-4-mediated and JAK/STAT1-dependent pathway.
The results of the present study indicated that sugar can enhance UPEC infection in uroepithelial cells by up-regulating the transduced circuit between TLR-4-mediated UPEC interaction and JAK/STAT-1 signal pathways. The results of the inhibitor-co-incubating experiments demonstrated that the mechanism involved in the synergistic amplification of TLR-4-mediated UPEC interaction and JAK/STAT1 signaling pathways is responsible for the increased UPEC infection in uroepithelial cells.
The results also proved that STAT-1 plays a critical role in the regulation of UPEC invasion and infection in the uroepithelial cells, especially those pretreated with glucose. The present study suggests a possible therapeutic approach to preferentially suppress UPEC infection during UTIs in the patients with diabetes.
与非糖尿病患者相比，糖尿病患者尿路感染（UTI）的发生率更高、病情更严重、持续时间更长。这导致了在肠杆菌科细菌（UPEC）感染时出现更复杂的病因。然而，关于其分子机制的研究还很少。
本研究（1）旨在验证糖是否会影响 UPEC 诱导的膀胱炎和侵袭泌尿道上皮细胞的过程，（2）阐述了糖增强 UPEC 感染泌尿道上皮细胞的作用机制与 TLR-4 介导和 JAK/STAT1 依赖性途径有关。
本研究结果表明，糖可以通过上调 TLR-4 介导的 UPEC 相互作用和 JAK/STAT-1 信号通路之间的转导回路，增强 UPEC 在上皮细胞中的感染。抑制剂共孵育实验的结果表明，TLR-4 介导的 UPEC 相互作用和 JAK/STAT1 信号通路协同放大的机制是导致上皮细胞中 UPEC 感染增加的原因。
结果还证明 STAT-1 在调节 UPEC 侵袭和感染泌尿道上皮细胞中起着关键作用，尤其是在葡萄糖预处理的情况下。本研究提示了一种可能的治疗方法，即在糖尿病患者发生 UTI 时，优先抑制 UPEC 感染。
