Untargeted metabolomic and proteomic analysis implicates SIRT2 as a novel therapeutic target for diabetic nephropathy
Abstract Diabetic nephropathy (DN) is one of the major causes of end-stage renal disease. This study aimed to explore the internal relationship between metabolic processes and autoimmune responses in patients with DN via untargeted metabolomics and Olink proteomics. The serum of 10 patients who were...
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| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-80492-1 |
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| author | Ruijing Zhang Runze Chang Heng Wang Jinshan Chen Chuanlong Lu Keyi Fan Yuhang Zhang Lizheng Li Sheng Yan Honglin Dong |
| author_facet | Ruijing Zhang Runze Chang Heng Wang Jinshan Chen Chuanlong Lu Keyi Fan Yuhang Zhang Lizheng Li Sheng Yan Honglin Dong |
| author_sort | Ruijing Zhang |
| collection | DOAJ |
| description | Abstract Diabetic nephropathy (DN) is one of the major causes of end-stage renal disease. This study aimed to explore the internal relationship between metabolic processes and autoimmune responses in patients with DN via untargeted metabolomics and Olink proteomics. The serum of 10 patients who were diagnosed with DN and 10 healthy individuals via untargeted metabolomics and Olink proteomics. Animal models were used to validate the characterized genes. Correlation analysis of major differentially abundant metabolites and differentially expressed proteins revealed that SIRT2 might be a key hub linking energy metabolism and innate immune responses. KEGG enrichment analysis showed that HIF-1 signaling pathway and renal cell carcinoma pathway were co-enriched pathways in energy metabolism and inflammatory response. VEGFA plays a vital role in these two signaling pathways. The ability of SIRT2 to regulate VEGFA expression has been demonstrated. In vivo experiments revealed that SIRT2, VEGFA, and HIF-1α were highly expressed in the kidneys of mice with diabetic nephropathy. In conclusion, our study combines metabolomics and proteomics to provide valuable insights into the synergistic roles of metabolic disorders and inflammatory responses in DN. The data suggest that SIRT2 may be a key target affecting these processes. |
| format | Article |
| id | doaj-art-3f5dfeab49b94be5928955eaea65545c |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-3f5dfeab49b94be5928955eaea65545c2025-02-09T12:36:42ZengNature PortfolioScientific Reports2045-23222025-02-0115111710.1038/s41598-024-80492-1Untargeted metabolomic and proteomic analysis implicates SIRT2 as a novel therapeutic target for diabetic nephropathyRuijing Zhang0Runze Chang1Heng Wang2Jinshan Chen3Chuanlong Lu4Keyi Fan5Yuhang Zhang6Lizheng Li7Sheng Yan8Honglin Dong9Department of Nephrology, The Second Hospital of Shanxi Medical UniversityDepartment of Vascular Surgery, The Second Hospital of Shanxi Medical UniversityDepartment of Vascular Surgery, The Second Hospital of Shanxi Medical UniversityDepartment of Vascular Surgery, The Second Hospital of Shanxi Medical UniversityDepartment of Vascular Surgery, The Second Hospital of Shanxi Medical UniversityDepartment of Vascular Surgery, The Second Hospital of Shanxi Medical UniversityDepartment of Vascular Surgery, The Second Hospital of Shanxi Medical UniversityDepartment of Vascular Surgery, The Second Hospital of Shanxi Medical UniversityDepartment of Vascular Surgery, The Second Hospital of Shanxi Medical UniversityDepartment of Vascular Surgery, The Second Hospital of Shanxi Medical UniversityAbstract Diabetic nephropathy (DN) is one of the major causes of end-stage renal disease. This study aimed to explore the internal relationship between metabolic processes and autoimmune responses in patients with DN via untargeted metabolomics and Olink proteomics. The serum of 10 patients who were diagnosed with DN and 10 healthy individuals via untargeted metabolomics and Olink proteomics. Animal models were used to validate the characterized genes. Correlation analysis of major differentially abundant metabolites and differentially expressed proteins revealed that SIRT2 might be a key hub linking energy metabolism and innate immune responses. KEGG enrichment analysis showed that HIF-1 signaling pathway and renal cell carcinoma pathway were co-enriched pathways in energy metabolism and inflammatory response. VEGFA plays a vital role in these two signaling pathways. The ability of SIRT2 to regulate VEGFA expression has been demonstrated. In vivo experiments revealed that SIRT2, VEGFA, and HIF-1α were highly expressed in the kidneys of mice with diabetic nephropathy. In conclusion, our study combines metabolomics and proteomics to provide valuable insights into the synergistic roles of metabolic disorders and inflammatory responses in DN. The data suggest that SIRT2 may be a key target affecting these processes.https://doi.org/10.1038/s41598-024-80492-1Diabetic nephropathy (DN)SerumUntargeted metabolomicsOlink proteomicsInflammation |
| spellingShingle | Ruijing Zhang Runze Chang Heng Wang Jinshan Chen Chuanlong Lu Keyi Fan Yuhang Zhang Lizheng Li Sheng Yan Honglin Dong Untargeted metabolomic and proteomic analysis implicates SIRT2 as a novel therapeutic target for diabetic nephropathy Scientific Reports Diabetic nephropathy (DN) Serum Untargeted metabolomics Olink proteomics Inflammation |
| title | Untargeted metabolomic and proteomic analysis implicates SIRT2 as a novel therapeutic target for diabetic nephropathy |
| title_full | Untargeted metabolomic and proteomic analysis implicates SIRT2 as a novel therapeutic target for diabetic nephropathy |
| title_fullStr | Untargeted metabolomic and proteomic analysis implicates SIRT2 as a novel therapeutic target for diabetic nephropathy |
| title_full_unstemmed | Untargeted metabolomic and proteomic analysis implicates SIRT2 as a novel therapeutic target for diabetic nephropathy |
| title_short | Untargeted metabolomic and proteomic analysis implicates SIRT2 as a novel therapeutic target for diabetic nephropathy |
| title_sort | untargeted metabolomic and proteomic analysis implicates sirt2 as a novel therapeutic target for diabetic nephropathy |
| topic | Diabetic nephropathy (DN) Serum Untargeted metabolomics Olink proteomics Inflammation |
| url | https://doi.org/10.1038/s41598-024-80492-1 |
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