Zhang Ruijing, Chang Runze, Wang Heng, Chen Jinshan, Lu Chuanlong, Fan Keyi, Zhang Yuhang, Li Lizheng, Yan Sheng, Dong Honglin
Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China.
Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Wuyi Road No. 382, Taiyuan, 030001, Shanxi, People's Republic of China.
Sci Rep. 2025 Feb 4;15(1):4236. doi: 10.1038/s41598-024-80492-1.
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.
糖尿病肾病（DN）是终末期肾病的主要病因之一。本研究旨在通过非靶向代谢组学和Olink蛋白质组学探索DN患者代谢过程与自身免疫反应之间的内在关系。通过非靶向代谢组学和Olink蛋白质组学分析了10例经诊断患有DN的患者和10例健康个体的血清。使用动物模型验证所鉴定的基因。主要差异丰富代谢物和差异表达蛋白质的相关性分析表明，SIRT2可能是连接能量代谢和先天性免疫反应的关键枢纽。KEGG富集分析表明，缺氧诱导因子-1（HIF-1）信号通路和肾细胞癌通路是能量代谢和炎症反应中的共同富集通路。血管内皮生长因子A（VEGFA）在这两条信号通路中起重要作用。已证实SIRT2具有调节VEGFA表达的能力。体内实验表明，SIRT2、VEGFA和HIF-1α在糖尿病肾病小鼠的肾脏中高表达。总之，我们的研究结合代谢组学和蛋白质组学，为代谢紊乱和炎症反应在DN中的协同作用提供了有价值的见解。数据表明，SIRT2可能是影响这些过程的关键靶点。
