Chen Hanzhi, Zhang Zhijian, Zhou Leting, Cai Ting, Liu Bin, Wang Liang, Yang Junwei
Center for Kidney Disease, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Nephrology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.
Front Genet. 2022 Feb 9;13:830437. doi: 10.3389/fgene.2022.830437. eCollection 2022.
Diabetic nephropathy (DN) is one of the major microvascular complications in diabetic patients and the leading cause of end-stage renal disease (ESRD). Previous studies found that immune-related genes and immune cell infiltration play important roles in the pathogenesis and development of DN. Therefore, this study aimed to explore immune-related biomarkers in DN. In this research, three microarray datasets that included 18 DN and 28 healthy tubule samples were downloaded and integrated as the training set to identify differentially expressed immune-related genes (DEIGs). A total of 63 DEIGs were identified, and most upregulated DEIGs were primarily involved in the inflammatory response and chemokine-mediated signaling pathways. The Microenvironment Cell Populations-counter (MCP-counter) algorithm was then used to estimate the abundance of infiltrated immune and stromal cell populations. According to DEIG, weighted gene coexpression network and protein-protein network analyses, CCL19 was identified as the hub immune-related biomarker. Moreover, the upregulated level of CCL19 was confirmed in other independent datasets as well as in experiments with high glucose. In summary, this study provides novel insights into the pathogenesis of diabetic nephropathy and identifies CCL19 as a potential critical gene of DN.
糖尿病肾病(DN)是糖尿病患者主要的微血管并发症之一,也是终末期肾病(ESRD)的主要病因。以往研究发现,免疫相关基因和免疫细胞浸润在DN的发病机制和发展过程中起重要作用。因此,本研究旨在探索DN中的免疫相关生物标志物。在本研究中,下载了三个包含18个DN小管样本和28个健康小管样本的微阵列数据集,并将其整合为训练集,以识别差异表达的免疫相关基因(DEIGs)。共鉴定出63个DEIGs,大多数上调的DEIGs主要参与炎症反应和趋化因子介导的信号通路。然后使用微环境细胞群体计数器(MCP-counter)算法来估计浸润的免疫细胞和基质细胞群体的丰度。根据DEIG、加权基因共表达网络和蛋白质-蛋白质网络分析,CCL19被确定为核心免疫相关生物标志物。此外,CCL19的上调水平在其他独立数据集中以及高糖实验中也得到了证实。总之,本研究为糖尿病肾病的发病机制提供了新的见解,并确定CCL19为DN的潜在关键基因。