Cao Haiyan, Rao Xiaosheng, Jia Junya, Yan Tiekun, Li Dong
Department of Nephrology, Tianjin Medical University General Hospital, Tianjin, China.
Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Front Pharmacol. 2022 Aug 17;13:932205. doi: 10.3389/fphar.2022.932205. eCollection 2022.
Diabetic kidney disease (DKD) is a major complication of diabetes mellitus, and the leading contributor of end-stage renal disease. Hence, insights into the molecular pathogenesis of DKD are urgently needed. The purpose of this article is to reveal the molecular mechanisms underlying the pathogenesis of DKD. The microarray datasets of GSE30528 and GSE30529 were downloaded from the NCBI Gene Expression Omnibus (GEO) database to identify the common differentially expressed genes (DEGs) between the glomerular DKD (GDKD) and tubular DKD (TDKD), respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to analyze the function and pathways of the common DEGs. After constructing the protein-protein interaction (PPI) network and subnetwork analysis, three types of analyses were performed, namely, identification of hub genes, analysis of the coexpressed network, and exploration of transcription factors (TFs). Totally, 348 and 463 DEGs were identified in GDKD and TDKD, respectively. Then, 66 common DEGs (63 upregulated DEGs and three downregulated DEGs) were obtained in DKD patients. GO and KEGG pathway analyses revealed the importance of inflammation response, immune-related pathways, and extracellular matrix-related pathways, especially chemokines and cytokines, in DKD. Fifteen hub genes from the 66 common DEGs, namely, IL10RA, IRF8, LY86, C1QA, C1QB, CD53, CD1C, CTSS, CCR2, CD163, CCL5, CD48, RNASE6, CD52, and CD2 were identified. In summary, through the microarray data analysis, the common functions and hub genes greatly contribute to the elucidation of the molecular pathogenesis associated with DKD.
糖尿病肾病（DKD）是糖尿病的主要并发症，也是终末期肾病的主要原因。因此，迫切需要深入了解DKD的分子发病机制。本文旨在揭示DKD发病机制背后的分子机制。从NCBI基因表达综合数据库（GEO）下载了GSE30528和GSE30529的微阵列数据集，分别用于鉴定肾小球DKD（GDKD）和肾小管DKD（TDKD）之间的共同差异表达基因（DEG）。进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析，以分析共同DEG的功能和通路。构建蛋白质-蛋白质相互作用（PPI）网络并进行子网分析后，进行了三种类型的分析，即枢纽基因鉴定、共表达网络分析和转录因子（TF）探索。在GDKD和TDKD中分别鉴定出348个和463个DEG。然后，在DKD患者中获得了66个共同DEG（63个上调DEG和3个下调DEG）。GO和KEGG通路分析揭示了炎症反应、免疫相关通路和细胞外基质相关通路，尤其是趋化因子和细胞因子，在DKD中的重要性。从66个共同DEG中鉴定出15个枢纽基因，即IL10RA、IRF8、LY86、C1QA、C1QB、CD53、CD1C、CTSS、CCR2、CD163、CCL5、CD48、RNASE6、CD52和CD2。总之，通过微阵列数据分析，共同功能和枢纽基因极大地有助于阐明与DKD相关的分子发病机制。
