Mesh : Humans Diabetic Nephropathies / genetics Serpin E2 Kidney Glomerulus Biomarkers Computational Biology Diabetes Mellitus ras GTPase-Activating Proteins

来  源:   DOI:10.1155/2024/5560922   PDF(Pubmed)

Abstract:
UNASSIGNED: Cellular senescence is thought to play a significant role in the onset and development of diabetic nephropathy. The goal of this study was to explore potential biomarkers associated with diabetic glomerulopathy from the perspective of senescence.
UNASSIGNED: Datasets about human glomerular biopsy samples related to diabetic nephropathy were systematically obtained from the Gene Expression Omnibus database. Hub senescence-associated genes were investigated by differential gene analysis and Least Absolute Shrinkage and Selection Operator analysis. Cluster analysis was employed to identify senescence molecular subtypes. A single-cell dataset was used to validate the above findings and further evaluate the senescence environment. The relationship between these genes and the glomerular filtration rate was explored based on the Nephroseq database. These gene expressions have also been explored in various kidney diseases.
UNASSIGNED: Twelve representative senescence-associated genes (VEGFA, IQGAP2, JUN, PLAT, ETS2, ANG, MMP14, VEGFC, SERPINE2, CXCR2, PTGES, and EGF) were finally identified. Biological changes in immune inflammatory response, cell cycle regulation, metabolic regulation, and immune microenvironment have been observed across different molecular subtypes. The above results were also validated based on single-cell analysis. Additionally, we also identified several significantly altered cell communication pathways, including COLLAGEN, PTN, LAMININ, SPP1, and VEGF. Finally, almost all these genes could well predict the occurrence of diabetic glomerulopathy based on receiver operating characteristic analysis and are associated with the glomerular filtration rate. These genes are differently expressed in various kidney diseases.
UNASSIGNED: The present study identified potential senescence-associated biomarkers and further explored the heterogeneity of diabetic glomerulopathy that might provide new insights into the diagnosis, assessment, management, and personalized treatment of DN.
摘要:
细胞衰老被认为在糖尿病肾病的发生和发展中起重要作用。这项研究的目的是从衰老的角度探索与糖尿病肾病相关的潜在生物标志物。
从基因表达综合数据库系统地获得与糖尿病肾病相关的人肾小球活检样品的数据集。通过差异基因分析和最小绝对收缩和选择算子分析研究了集线器衰老相关基因。采用聚类分析鉴定衰老分子亚型。使用单细胞数据集来验证上述发现并进一步评估衰老环境。基于Nephroseq数据库探索这些基因与肾小球滤过率之间的关系。这些基因表达也已在各种肾脏疾病中进行了探索。
十二个代表性衰老相关基因(VEGFA,IQGAP2,JUN,PLAT,ETS2,ANG,MMP14,VEGFC,SERPINE2,CXCR2,PTGES,和EGF)最终确定。免疫炎症反应的生物学变化,细胞周期调节,代谢调节,和免疫微环境已经在不同的分子亚型中观察到。以上结果也基于单细胞分析进行了验证。此外,我们还发现了几种显著改变的细胞通讯通路,包括胶原蛋白,PTN,Laminin,SPP1和VEGF。最后,基于受试者工作特性分析,几乎所有这些基因都能很好地预测糖尿病肾病的发生,并与肾小球滤过率相关。这些基因在各种肾脏疾病中表达不同。
本研究确定了潜在的衰老相关生物标志物,并进一步探索了糖尿病肾病的异质性,这可能为诊断提供新的见解。评估,管理,以及DN的个性化治疗。
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