Transcriptomic Redox Dysregulation in a Rat Model of Metabolic Syndrome-Associated Kidney Injury
Metabolic syndrome (MetS), characterized by obesity, insulin resistance, and dyslipidemia, is a major risk factor for renal injury. Oxidative stress (OxS) plays a pivotal role in its progression; however, the underlying molecular mechanisms are not fully understood. In this study, we established a r...
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MDPI AG
2025-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/14/6/746 |
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| author | Chien-Lin Lu Yi-Yun Wang Yih-Jeng Tsai Hsuan-Ting Chen Ming-Chieh Ma Wen-Bin Wu |
| author_facet | Chien-Lin Lu Yi-Yun Wang Yih-Jeng Tsai Hsuan-Ting Chen Ming-Chieh Ma Wen-Bin Wu |
| author_sort | Chien-Lin Lu |
| collection | DOAJ |
| description | Metabolic syndrome (MetS), characterized by obesity, insulin resistance, and dyslipidemia, is a major risk factor for renal injury. Oxidative stress (OxS) plays a pivotal role in its progression; however, the underlying molecular mechanisms are not fully understood. In this study, we established a rat model of MetS using a high-fat diet combined with a single-dose streptozotocin injection in male Wistar rats. MetS rats exhibited systemic OxS, evidenced by elevated circulating levels of free oxygen radicals and decreased antioxidant defense capacity, as well as hypertension, renal lipid peroxidation, glomerular hyperfiltration, and renal tubular injury. Transcriptomic profiling of renal tissue revealed significant downregulation of six OxS-related genes: C-C motif chemokine ligand 5 (CCL5), glutamate-cysteine ligase catalytic subunit, glutathione peroxidase 6, recombination activating gene 2, NAD(P)H: quinone oxidoreductase 1, and selenoprotein P-1. Among these downregulated genes, CCL5 was further confirmed to be repressed at both mRNA and protein levels across intrarenal and systemic compartments. Given its documented functions in immune signaling and redox homeostasis, CCL5 downregulation may contribute to enhanced oxidative damage in MetS-associated renal injury. These findings highlight the role of redox gene dysregulation in the pathogenesis of MetS-related kidney disease and support the potential of CCL5 as a biomarker for oxidative renal injury. |
| format | Article |
| id | doaj-art-8d08a393b2734727a609e7ce54079d38 |
| institution | OA Journals |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-8d08a393b2734727a609e7ce54079d382025-08-20T02:24:30ZengMDPI AGAntioxidants2076-39212025-06-0114674610.3390/antiox14060746Transcriptomic Redox Dysregulation in a Rat Model of Metabolic Syndrome-Associated Kidney InjuryChien-Lin Lu0Yi-Yun Wang1Yih-Jeng Tsai2Hsuan-Ting Chen3Ming-Chieh Ma4Wen-Bin Wu5School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242062, TaiwanGraduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 242062, TaiwanSchool of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242062, TaiwanSchool of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242062, TaiwanSchool of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242062, TaiwanSchool of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 242062, TaiwanMetabolic syndrome (MetS), characterized by obesity, insulin resistance, and dyslipidemia, is a major risk factor for renal injury. Oxidative stress (OxS) plays a pivotal role in its progression; however, the underlying molecular mechanisms are not fully understood. In this study, we established a rat model of MetS using a high-fat diet combined with a single-dose streptozotocin injection in male Wistar rats. MetS rats exhibited systemic OxS, evidenced by elevated circulating levels of free oxygen radicals and decreased antioxidant defense capacity, as well as hypertension, renal lipid peroxidation, glomerular hyperfiltration, and renal tubular injury. Transcriptomic profiling of renal tissue revealed significant downregulation of six OxS-related genes: C-C motif chemokine ligand 5 (CCL5), glutamate-cysteine ligase catalytic subunit, glutathione peroxidase 6, recombination activating gene 2, NAD(P)H: quinone oxidoreductase 1, and selenoprotein P-1. Among these downregulated genes, CCL5 was further confirmed to be repressed at both mRNA and protein levels across intrarenal and systemic compartments. Given its documented functions in immune signaling and redox homeostasis, CCL5 downregulation may contribute to enhanced oxidative damage in MetS-associated renal injury. These findings highlight the role of redox gene dysregulation in the pathogenesis of MetS-related kidney disease and support the potential of CCL5 as a biomarker for oxidative renal injury.https://www.mdpi.com/2076-3921/14/6/746C-C motif chemokine ligand 5glomerular hyperfiltrationlipid peroxidationoxidative stress-related gene profiling |
| spellingShingle | Chien-Lin Lu Yi-Yun Wang Yih-Jeng Tsai Hsuan-Ting Chen Ming-Chieh Ma Wen-Bin Wu Transcriptomic Redox Dysregulation in a Rat Model of Metabolic Syndrome-Associated Kidney Injury Antioxidants C-C motif chemokine ligand 5 glomerular hyperfiltration lipid peroxidation oxidative stress-related gene profiling |
| title | Transcriptomic Redox Dysregulation in a Rat Model of Metabolic Syndrome-Associated Kidney Injury |
| title_full | Transcriptomic Redox Dysregulation in a Rat Model of Metabolic Syndrome-Associated Kidney Injury |
| title_fullStr | Transcriptomic Redox Dysregulation in a Rat Model of Metabolic Syndrome-Associated Kidney Injury |
| title_full_unstemmed | Transcriptomic Redox Dysregulation in a Rat Model of Metabolic Syndrome-Associated Kidney Injury |
| title_short | Transcriptomic Redox Dysregulation in a Rat Model of Metabolic Syndrome-Associated Kidney Injury |
| title_sort | transcriptomic redox dysregulation in a rat model of metabolic syndrome associated kidney injury |
| topic | C-C motif chemokine ligand 5 glomerular hyperfiltration lipid peroxidation oxidative stress-related gene profiling |
| url | https://www.mdpi.com/2076-3921/14/6/746 |
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