Yao Xinyue, Shen Hong, Cao Fukai, He Hailan, Li Boyu, Zhang Haojun, Zhang Xinduo, Li Zhiguo
The Hebei Key Lab for Organ Fibrosis, The Hebei Key Lab for Chronic Disease, School of Public Health, International Science and Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan, China.
Department of Modern Technology and Education Center, North China University of Science and Technology, Tangshan, China.
Front Med (Lausanne). 2021 Jun 24;8:657918. doi: 10.3389/fmed.2021.657918. eCollection 2021.
Diabetic nephropathy (DN) is the main cause of end stage renal disease (ESRD). Glomerulus damage is one of the primary pathological changes in DN. To reveal the gene expression alteration in the glomerulus involved in DN development, we screened the Gene Expression Omnibus (GEO) database up to December 2020. Eleven gene expression datasets about gene expression of the human DN glomerulus and its control were downloaded for further bioinformatics analysis. By using R language, all expression data were extracted and were further cross-platform normalized by Shambhala. Differentially expressed genes (DEGs) were identified by Student's -test coupled with false discovery rate (FDR) ( < 0.05) and fold change (FC) ≥1.5. DEGs were further analyzed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID) to enrich the Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. We further constructed a protein-protein interaction (PPI) network of DEGs to identify the core genes. We used digital cytometry software CIBERSORTx to analyze the infiltration of immune cells in DN. A total of 578 genes were identified as DEGs in this study. Thirteen were identified as core genes, in which , and were seldom linked with DN. Based on the result of GO, KEGG enrichment, and CIBERSORTx immune cells infiltration analysis, we hypothesize that positive feedback may form among the glomerulus, platelets, and immune cells. This vicious cycle may damage the glomerulus persistently even after the initial high glucose damage was removed. Studying the genes and pathway reported in this study may shed light on new knowledge of DN pathogenesis.
糖尿病肾病（DN）是终末期肾病（ESRD）的主要原因。肾小球损伤是DN的主要病理变化之一。为揭示参与DN发生发展的肾小球基因表达改变，我们检索了截至2020年12月的基因表达综合数据库（GEO）。下载了11个人类DN肾小球及其对照的基因表达数据集用于进一步的生物信息学分析。使用R语言提取所有表达数据，并通过Shambhala进行进一步的跨平台标准化。通过Student's t检验结合错误发现率（FDR）（<0.05）和变化倍数（FC）≥1.5来鉴定差异表达基因（DEG）。通过注释、可视化和综合发现数据库（DAVID）对DEG进行进一步分析，以富集基因本体论（GO）术语和京都基因与基因组百科全书（KEGG）通路。我们进一步构建了DEG的蛋白质-蛋白质相互作用（PPI）网络以鉴定核心基因。我们使用数字细胞计数软件CIBERSORTx分析DN中免疫细胞的浸润情况。本研究共鉴定出578个基因作为DEG。其中13个被鉴定为核心基因，其中，和与DN的关联很少。基于GO、KEGG富集以及CIBERSORTx免疫细胞浸润分析的结果，我们推测在肾小球、血小板和免疫细胞之间可能形成正反馈。即使在最初的高糖损伤消除后，这种恶性循环仍可能持续损害肾小球。研究本研究中报道的基因和通路可能为DN发病机制的新知识提供线索。
