Chen-Hsun Ho1, Chia-Kwung Fan2, Chia-Chang Wu1, Hong-Jeng Yu3, Hsin-Tien Liu4, Kuan-Chou Chen1, Shih-Ping Liu5, Po-Ching Cheng6. 1. 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. 2. 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. 3. Department of Urology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan. 4. Department of Molecular Parasitology and Tropical Diseases, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 5. Department of Urology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan. Electronic address: spliu@ntuh.gov.tw. 6. 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. Electronic address: bonjovi@tmu.edu.tw.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.