Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Linkou, Taiwan; Graduate Institute of Biomedical Sciences, Department of Microbiology and Immunology, Department of Biochemistry, Chang Gung University, Taoyuan, Taiwan.
Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
Genomics. 2023 May;115(3):110624. doi: 10.1016/j.ygeno.2023.110624. Epub 2023 Apr 14.
Leptospirosis can cause chronic kidney damage, putting patients at risk of additional kidney injury due to other factors that can lead to renal failure. To understand the combined effect, the transcriptome profiles of kidneys of mice with adenine-induced and chronically Leptospira-infected kidneys were analysed. Chronic inflammation and T-helper 17 immune responses were activated and a high-level expression of Indoleamine 2,3-dioxygenase 1 protein was found. The results indicate that the combination may predispose patients to chronic inflammation, kidney function disruption, and symptoms seen in progressive chronic kidney disease (CKD). Furthermore, immunometabolic regulation may contribute to renal injury caused by chronic leptospirosis with secondary nephrotoxic injury. This study identified several significantly disrupted genes that could serve as potential targets for the diagnosis or treatment of CKD. Our work provides insight into the combined effect of leptospirosis and secondary kidney damage and the molecular basis for rapid progression of CKD.
钩端螺旋体病可导致慢性肾脏损伤,使患者因其他可能导致肾衰竭的因素而面临额外的肾脏损伤风险。为了了解联合作用,分析了腺嘌呤诱导和慢性钩端螺旋体感染的小鼠肾脏的转录组谱。慢性炎症和辅助性 T 细胞 17 免疫反应被激活,并且发现吲哚胺 2,3-双加氧酶 1 蛋白高水平表达。结果表明,这种组合可能使患者易患慢性炎症、肾功能障碍以及进行性慢性肾脏病 (CKD) 中出现的症状。此外,免疫代谢调节可能导致继发于肾毒性损伤的慢性钩端螺旋体病引起的肾损伤。本研究鉴定了几个显著失调的基因,这些基因可能成为 CKD 诊断或治疗的潜在靶点。我们的工作深入了解了钩端螺旋体病和继发性肾脏损伤的联合作用以及 CKD 快速进展的分子基础。