Transcriptome landscape reveals the chronic inflammatory response in kidneys affected by the combinatory effect of leptospirosis and nephrotoxic injury

Li-Fang Chou; Chih-Wei Huang; Huang-Yu Yang; Ya-Chung Tian; Ming-Yang Chang; Cheng-Chieh Hung; Kuan-Hsing Chen; Shen-Hsing Hsu; Chung-Ying Tsai; Yi-Ching Ko; Ting-Wen Chen; Chih-Wei Yang

doi:10.1016/j.ygeno.2023.110624

Transcriptome landscape reveals the chronic inflammatory response in kidneys affected by the combinatory effect of leptospirosis and nephrotoxic injury

Genomics. 2023 May;115(3):110624. doi: 10.1016/j.ygeno.2023.110624. Epub 2023 Apr 14.

Authors

Affiliations

¹ 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.
² Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
³ Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Linkou, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
⁴ Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Linkou, Taiwan.
⁵ Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan; Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan; Center for Intelligent Drug Systems and Smart Bio-devices (IDS(2)B), National Yang Ming Chiao Tung University, Hsinchu;, Taiwan. Electronic address: dodochen@nctu.edu.tw.
⁶ Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Linkou, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address: cwyang@ms1.hinet.net.

PMID: 37062365
DOI: 10.1016/j.ygeno.2023.110624

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.

Keywords: Adenine; Chronic kidney disease; Combinatory effect; Leptospirosis; Renal transcriptome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Infective Agents*
Inflammation
Kidney
Leptospirosis* / complications
Mice
Renal Insufficiency, Chronic* / complications
Transcriptome

Substances

Anti-Infective Agents