糖尿病肾病诊断标志物与潜在治疗小分子药物的预测研究
Prediction of Diagnostic Markers and Potential Therapeutic Small-Molecule Drugs for Diabetic Nephropathy
DOI: 10.12677/hjbm.2026.162033, PDF,    科研立项经费支持
作者: 夏一玮*, 黄敬婷*, 李 慧, 汪 艺：桂林医科大学检验与生物技术学院，广西 桂林；蔡乐盈：桂林医科大学第一临床医学院，广西 桂林；吴群英#：桂林医科大学基础医学院，广西 桂林
关键词: 糖尿病肾病；分泌蛋白；生物信息学；CD44；Diabetic Nephropathy； Secretory Protein； Bioinformatics； CD44
摘要: 糖尿病肾病(diabetic nephropathy, DN)作为终末期肾病的主要病因之一，其早期诊断方法并不十分有效。本研究从GEO数据库和人类蛋白质图谱(human protein atlas, HPA)数据库中获取糖尿病肾病(diabetic nephropathy, DN)表达谱数据和编码分泌蛋白的基因，通过差异表达分析鉴定出57个差异表达的分泌蛋白相关基因(differential expression-secreted protein genes, DE-SPGs)。功能富集分析显示这些基因显著富集于体液免疫、ECM-受体相互作用等信号通路。进一步通过蛋白质–蛋白质相互作用网络(protein-protein interaction network, PPI)分析，筛选出4个候选关键基因，其中CD44在外部组织验证集(GSE96084)和血液验证集(GSE142153)中均一致高表达，并表现出良好的诊断性能，其表达与肾小球滤过率水平显著负相关、与体内血肌酐水平显著正相关。本研究表明CD44基因有望成为糖尿病肾病诊断相关生物标志物，为深入理解DN肾功能障碍的发生与发展和开发临床干预策略提供新思路。
Abstract: Diabetic nephropathy (DN), as one of the primary causes of end-stage renal disease, lacks effective early diagnostic methods. This study obtained expression profile data and genes encoding secreted proteins for diabetic nephropathy (DN) from the GEO database and the Human Protein Atlas (HPA) database. Through differential expression analysis, 57 differentially expressed secreted protein-related genes (DE-SPGs) were identified. Functional enrichment analysis revealed that these genes were significantly enriched in pathways such as humoral immunity and ECM-receptor interactions. Further analysis via the protein-protein interaction network (PPI) identified four candidate key genes. Among them, CD44 was consistently overexpressed in both the external tissue validation set (GSE96084) and the blood validation set (GSE142153), demonstrating good diagnostic performance. It showed a negative correlation trend with glomerular filtration rate levels and a positive correlation trend with serum creatinine levels in vivo. This study indicates that the CD44 gene has the potential to become a diagnostic biomarker for diabetic nephropathy, providing a new direction for deepening the understanding of the occurrence and development of renal dysfunction in DN and for developing clinical intervention strategies.
文章引用：夏一玮, 黄敬婷, 蔡乐盈, 李慧, 汪艺, 吴群英. 糖尿病肾病诊断标志物与潜在治疗小分子药物的预测研究[J]. 生物医学, 2026, 16(2): 323-331. https://doi.org/10.12677/hjbm.2026.162033

参考文献

[1] Shan, S., Luo, Z., Yao, L., Zhou, J., Wu, J., Jiang, D., et al. (2024) Cross‐Country Inequalities in Disease Burden and Care Quality of Chronic Kidney Disease Due to Type 2 Diabetes Mellitus, 1990-2021: Findings from the Global Burden of Disease Study 2021. Diabetes, Obesity and Metabolism, 26, 5950-5959. [Google Scholar] [CrossRef] [PubMed]
[2] Li, Z., Feng, J., Zhong, J., Lu, M., Gao, X. and Zhang, Y. (2022) Screening of the Key Genes and Signalling Pathways for Diabetic Nephropathy Using Bioinformatics Analysis. Frontiers in Endocrinology, 13, Article ID: 864407. [Google Scholar] [CrossRef] [PubMed]
[3] Samsu, N. (2021) Diabetic Nephropathy: Challenges in Pathogenesis, Diagnosis, and Treatment. BioMed Research International, 2021, Article ID: 1497449. [Google Scholar] [CrossRef] [PubMed]
[4] Jung, C. and Yoo, T. (2022) Pathophysiologic Mechanisms and Potential Biomarkers in Diabetic Kidney Disease. Diabetes & Metabolism Journal, 46, 181-197. [Google Scholar] [CrossRef] [PubMed]
[5] Neuen, B.L., Heerspink, H.J.L., Vart, P., Claggett, B.L., Fletcher, R.A., Arnott, C., et al. (2024) Estimated Lifetime Cardiovascular, Kidney, and Mortality Benefits of Combination Treatment with SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Nonsteroidal MRA Compared with Conventional Care in Patients with Type 2 Diabetes and Albuminuria. Circulation, 149, 450-462. [Google Scholar] [CrossRef] [PubMed]
[6] Tofte, N., Lindhardt, M., Adamova, K., Bakker, S.J.L., Beige, J., Beulens, J.W.J., et al. (2020) Early Detection of Diabetic Kidney Disease by Urinary Proteomics and Subsequent Intervention with Spironolactone to Delay Progression (PRIORITY): A Prospective Observational Study and Embedded Randomised Placebo-Controlled Trial. The Lancet Diabetes & Endocrinology, 8, 301-312. [Google Scholar] [CrossRef] [PubMed]
[7] Guillén-Gómez, E., Bardají-de-Quixano, B., Ferrer, S., Brotons, C., Knepper, M.A., Carrascal, M., et al. (2018) Urinary Proteome Analysis Identified Neprilysin and VCAM as Proteins Involved in Diabetic Nephropathy. Journal of Diabetes Research, 2018, Article ID: 6165303. [Google Scholar] [CrossRef] [PubMed]
[8] Liu, S., Gui, Y., Wang, M.S., Zhang, L., Xu, T., Pan, Y., et al. (2021) Serum Integrative Omics Reveals the Landscape of Human Diabetic Kidney Disease. Molecular Metabolism, 54, Article 101367. [Google Scholar] [CrossRef] [PubMed]
[9] Liu, W., Yuan, L., Che, M., Hou, S., Meng, F., Xu, D., et al. (2023) Exploring the Mechanism of Dahuang-Tusizi Drug Pair in the Treatment of Diabetes Nephropathy Based on Network Pharmacology and Immune Infiltration Analysis. Medicine, 102, e36196. [Google Scholar] [CrossRef] [PubMed]
[10] Donate-Correa, J., Luis-Rodríguez, D., Martín-Núñez, E., Tagua, V.G., Hernández-Carballo, C., Ferri, C., et al. (2020) Inflammatory Targets in Diabetic Nephropathy. Journal of Clinical Medicine, 9, Article 458. [Google Scholar] [CrossRef] [PubMed]
[11] Wang, X., Zhang, L., Huang, K., Lou, C., Xia, Y. and Zhou, Y. (2025) Costunolide Reduces DN Inflammatory Response and Renal Thrombosis by Inhibiting NET Formation. Journal of Diabetes Research, 2025, Article ID: 1159325. [Google Scholar] [CrossRef] [PubMed]
[12] He, Y., Liu, X., Wang, R., Pang, J., Tang, Z., Zhong, Q., et al. (2024) CD2 Glycoprotein and CD44 Structure and Prevention of Diabetes Nephropathy: Central Characteristics of Related Genes Based on WGCNA and PPI. International Journal of Biological Macromolecules, 279, Article 135393. [Google Scholar] [CrossRef] [PubMed]
[13] Huang, M., Chang, J., Liu, Y., Yin, J. and Zeng, X. (2025) Apelin/APJ Alleviates Diabetic Nephropathy by Improving Glomerular Endothelial Cells Dysfunction via SIRT3-Klf15. Molecular Medicine Reports, 31, 1-12. [Google Scholar] [CrossRef] [PubMed]
[14] Dong, R., Zhang, X., Liu, Y., Zhao, T., Sun, Z., Liu, P., et al. (2023) Rutin Alleviates EndMT by Restoring Autophagy through Inhibiting HDAC1 via PI3K/AKT/mTOR Pathway in Diabetic Kidney Disease. Phytomedicine, 112, Article 154700. [Google Scholar] [CrossRef] [PubMed]
[15] Wang, X., Jiang, L., Liu, X., Huang, Y., Wang, A., Zeng, H., et al. (2022) Paeoniflorin Binds to VEGFR2 to Restore Autophagy and Inhibit Apoptosis for Podocyte Protection in Diabetic Kidney Disease through PI3K-AKT Signaling Pathway. Phytomedicine, 106, Article 154400. [Google Scholar] [CrossRef] [PubMed]
[16] Huang, J., Meng, P., Liang, Y., Li, X., Zhou, S., Li, J., et al. (2025) Tubular CD44 Plays a Key Role in Aggravating AKI through NF-κB P65-Mediated Mitochondrial Dysfunction. Cell Death & Disease, 16, Article No. 119. [Google Scholar] [CrossRef] [PubMed]
[17] Ma, Z., Shi, S., Ren, M., Pang, C., Zhan, Y., An, H., et al. (2022) Molecular Mechanism of CD44 Homodimerization Modulated by Palmitoylation and Membrane Environments. Biophysical Journal, 121, 2671-2683. [Google Scholar] [CrossRef] [PubMed]
[18] Diwan, B., Yadav, R., Goyal, R. and Sharma, R. (2024) Sustained Exposure to High Glucose Induces Differential Expression of Cellular Senescence Markers in Murine Macrophages but Impairs Immunosurveillance Response to Senescent Cells Secretome. Biogerontology, 25, 627-647. [Google Scholar] [CrossRef] [PubMed]

为你推荐