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Updated: Aug 2, 2025

Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
Transcriptome landscape reveals the chronic inflammatory response in kidneys affected by the combinatory effect of
Li-Fang Chou1, Chih-Wei Huang2, Huang-Yu Yang3
1Kidney 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.
Abstract:
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.
Insights
Chronic leptospirosis combined with secondary kidney injury accelerates chronic kidney disease (CKD) progression. This study reveals key gene disruptions and immune pathways involved in this accelerated renal damage.
Area of Science:
- Nephrology
- Immunology
- Microbiology
Background:
- Leptospirosis can lead to chronic kidney damage.
- Secondary kidney injuries exacerbate renal failure risk in patients.
- Understanding combined insults is crucial for managing progressive chronic kidney disease (CKD).
Purpose of the Study:
- To investigate the combined effects of leptospirosis and secondary kidney injury on kidney transcriptome.
- To identify molecular mechanisms underlying accelerated CKD progression.
- To discover potential diagnostic or therapeutic targets for combined renal injury.
Main Methods:
- Transcriptome profiling of mouse kidneys.
- Analysis of adenine-induced and chronic Leptospira-infected kidney models.
- Assessment of gene expression and protein levels, including Indoleamine 2,3-dioxygenase 1.
Main Results:
- Combined injury activated chronic inflammation and T-helper 17 immune responses.
- High expression of Indoleamine 2,3-dioxygenase 1 protein was observed.
- Significant gene expression disruptions were identified, indicating predisposition to CKD symptoms.
Conclusions:
- The combination of leptospirosis and secondary nephrotoxic injury promotes chronic inflammation and kidney dysfunction.
- Immunometabolic dysregulation plays a role in the observed renal injury.
- Disrupted genes identified may serve as novel targets for CKD diagnosis and treatment.
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