Department of Hand Surgery, Wuhan Fourth Hospital; Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland).
Med Sci Monit. 2020 Dec 18;26:e928788. doi: 10.12659/MSM.928788.
BACKGROUND Diabetic wound (DW) treatment is a serious challenge for clinicians, and the underlying mechanisms of DWs remain elusive. We sought to identify the critical genes in the development of DWs and provide potential targets for DW therapies. MATERIAL AND METHODS Datasets of GSE38396 from the Gene Expression Omnibus (GEO) database were reviewed. Pathway analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology term analyses were carried out, and Cytoscape software (Cytoscape 3.7.2) was used to construct the protein interaction network. Serum samples from patients with diabetes and control participants were collected, and the expression of estrogen receptor 1 (ESR1) was measured by quantitative reverse-transcription polymerase chain reaction. In addition, the function of ESR1 in human skin fibroblasts was investigated in vitro. RESULTS Eight samples were analyzed using the Morpheus online tool, which identified 637 upregulated and 448 downregulated differentially expressed genes. The top 5 KEGG pathways of upregulated differentially expressed genes were associated with sphingolipid metabolism, estrogen signaling, ECM-receptor interaction, MAPK signaling, and PI3K-Akt signaling. The hub genes for DWs were JUN, ESR1, CD44, SMARCA4, MMP2, BMP4, GSK3B, WDR5, PTK2, and PTGS2. JUN, MMP2, and ESR1 were the upregulated hub genes, and ESR1 was found to be consistently enriched in DW patients. Inhibition of ESR1 had a stimulative role in human skin fibroblasts. CONCLUSIONS ESR1 was identified as a crucial gene in the development of DWs, which suggests potential therapeutic targets for DW healing.
糖尿病创面（DW）的治疗对临床医生来说是一个严峻的挑战，而 DW 的潜在机制仍难以捉摸。我们试图确定 DW 发展过程中的关键基因，并为 DW 治疗提供潜在靶点。
我们查阅了基因表达综合数据库（GEO）中 GSE38396 数据集。使用京都基因与基因组百科全书（KEGG）进行通路分析，进行基因本体论术语分析，并使用 Cytoscape 软件（Cytoscape 3.7.2）构建蛋白质相互作用网络。收集糖尿病患者和对照参与者的血清样本，通过定量逆转录聚合酶链反应测量雌激素受体 1（ESR1）的表达。此外，还在体外研究了 ESR1 在人皮肤成纤维细胞中的功能。
使用 Morpheus 在线工具分析了 8 个样本，鉴定出 637 个上调和 448 个下调的差异表达基因。上调差异表达基因的前 5 个 KEGG 通路与鞘脂代谢、雌激素信号、ECM-受体相互作用、MAPK 信号和 PI3K-Akt 信号有关。DW 的枢纽基因有 JUN、ESR1、CD44、SMARCA4、MMP2、BMP4、GSK3B、WDR5、PTK2 和 PTGS2。JUN、MMP2 和 ESR1 是上调的枢纽基因，而 ESR1 在 DW 患者中始终表现出富集。ESR1 的抑制对人皮肤成纤维细胞具有刺激作用。
ESR1 被确定为 DW 发展过程中的关键基因，这表明其可能成为 DW 愈合的治疗靶点。
