Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Division of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
Cell Tissue Res. 2024 Oct;398(1):27-33. doi: 10.1007/s00441-024-03908-4. Epub 2024 Aug 20.
Infections are common in patients with diabetes. Moreover, increasing incidence of antibiotic resistance impedes the complete bacterial clearance and calls for alternative treatment strategies. Along with antibacterial resistance, compromised host conditions create a favorable condition for the disease progression. In particular, cell junction proteins are of major importance as they contribute to a tight cell barrier, protecting against invading pathogens. However, the impact of high glucose on cell junction proteins has received little attention in the urinary bladder but merits closer investigation. Here, we report that during diabetes the expression of cell junction protein, claudin 14 is compromised in the human urine exfoliated cells and in the urinary bladder of type 2 diabetic mouse. Further in vitro analysis confirmed a direct correlation of lower intracellular calcium levels with claudin 14 expression in high glucose-treated human uroepithelial cells. Moreover, external calcium supplementation in high glucose-treated cells significantly affected the cell migration and restored the claudin 14 expression through focal adhesion and β-1 integrins. Strengthening the epithelial barrier is essential, especially in individuals with diabetes where basal calcium levels could contribute.
感染在糖尿病患者中很常见。此外,抗生素耐药性的不断增加阻碍了细菌的完全清除,并需要替代治疗策略。除了抗菌耐药性之外,宿主条件的恶化也为疾病的进展创造了有利条件。特别是细胞连接蛋白非常重要,因为它们有助于形成紧密的细胞屏障,防止入侵病原体。然而,高血糖对细胞连接蛋白的影响在膀胱中很少受到关注,但值得更深入的研究。在这里,我们报告在糖尿病中,人尿脱落细胞和 2 型糖尿病小鼠的膀胱中,细胞连接蛋白 Claudin 14 的表达受损。进一步的体外分析证实,在高葡萄糖处理的人尿路上皮细胞中,细胞内钙水平降低与 Claudin 14 表达直接相关。此外,在高葡萄糖处理的细胞中补充外钙会显著影响细胞迁移,并通过粘着斑和β-1 整合素恢复 Claudin 14 的表达。加强上皮屏障是至关重要的,特别是在基础钙水平可能起作用的糖尿病患者中。