鉴定与糖尿病肾小管间质损伤相关的转录因子。
Identification of transcription factors related to diabetic tubulointerstitial injury.
机构信息
Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.
Hunan Communication Polytechnic, Changsha, 410132, Hunan, China.
出版信息
J Transl Med. 2023 Mar 29;21(1):228. doi: 10.1186/s12967-023-04069-8.
BACKGROUND
Diabetic nephropathy (DN) is a main cause of chronic renal failure. Despite decades of extensive study, the molecular mechanisms underlying diabetic tubulointerstitial injury remain unclear. We aim to identify key transcription factor genes involved in diabetic tubulointerstitial injury.
METHODS
A microarray dataset (GSE30122) from Gene Expression Omnibus (GEO) was downloaded. A total of 38 transcription factor genes based on 166 differentially expressed genes (DEGs) were identified by UCSC_TFBS.
RESULTS
The regulatory network showed connections between the top 10 transcription factors and their target DEGs. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of targeted DEGs indicated that extracellular space, extracellular exosome, cell surface and complement and coagulation cascades were most significantly enriched. Utilizing Nephroseq v5 online platform, the mRNA expression pattern analysis of transcription factor genes demonstrated that mRNA expression of CDC5, CEBPA, FAC1, HFH1, IRF1, NFE2 and TGIF1 increased in renal tubulointerstitium of DN patients compared with normal controls while that of CEBPB and FOXO4 decreased in renal tubulointerstitium of DN patients compared with normal controls. Correlation analysis between mRNA expression of transcription factor genes in renal tubulointerstitium and clinical features showed that AP1, BACH1, CDC5, FAC1, FOXD1, FOXJ2, FOXO1, FOXO4, HFH1, IRF1, POU3F2, SOX5, SOX9, RSRFC4, S8 and TGIF1 may be related to diabetic tubulointerstitial injury.
CONCLUSIONS
(1) CDC5, FAC1, FOXO4, HFH1, IRF1 and TGIF1 may be key transcription factor genes. (2)Transcription factors involved in diabetic tubulointerstitial injury may become prospective targets for diagnosis and treatment of DN.
背景
糖尿病肾病（DN）是慢性肾衰竭的主要原因。尽管经过几十年的广泛研究，糖尿病肾小管间质损伤的分子机制仍不清楚。我们旨在确定参与糖尿病肾小管间质损伤的关键转录因子基因。
方法
从基因表达综合数据库（GEO）下载了一个微阵列数据集（GSE30122）。根据 166 个差异表达基因（DEGs），UCSC_TFBS 共鉴定出 38 个转录因子基因。
结果
调控网络显示了前 10 个转录因子与其靶 DEGs 之间的联系。靶 DEGs 的基因本体论（GO）富集和京都基因与基因组百科全书（KEGG）通路分析表明，细胞外空间、细胞外外泌体、细胞表面和补体与凝血级联反应最为显著富集。利用 Nephroseq v5 在线平台，对转录因子基因的 mRNA 表达模式分析表明，与正常对照组相比，DN 患者肾小管间质中 CDC5、CEBPA、FAC1、HFH1、IRF1、NFE2 和 TGIF1 的 mRNA 表达增加，而 CEBPB 和 FOXO4 的 mRNA 表达降低。转录因子基因在肾小管间质中的 mRNA 表达与临床特征的相关性分析表明，AP1、BACH1、CDC5、FAC1、FOXD1、FOXJ2、FOXO1、FOXO4、HFH1、IRF1、POU3F2、SOX5、SOX9、RSRFC4、S8 和 TGIF1 可能与糖尿病肾小管间质损伤有关。
结论
（1）CDC5、FAC1、FOXO4、HFH1、IRF1 和 TGIF1 可能是关键的转录因子基因。（2）参与糖尿病肾小管间质损伤的转录因子可能成为诊断和治疗 DN 的潜在靶点。
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