The First Hospital of Changsha, Changsha, 410005, China; The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, Changsha, 410008, China; Changsha Maternal and Child Health Hospital Affiliated to Hunan Normal University, Changsha, 410007, China.
The First Hospital of Changsha, Changsha, 410005, China; The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, Changsha, 410008, China.
Comput Biol Med. 2023 Jun;159:106858. doi: 10.1016/j.compbiomed.2023.106858. Epub 2023 Apr 13.
Foot ulcers are a common complication of diabetes mellitus, which is associated with high morbidity and mortality among diabetic patients. The present study aims to investigate novel wound healing pathways in diabetic foot ulcers (DFU) through proteomics and a network pharmacology analysis. Tandem mass tag (TMT) labeled quantitative proteomics method was performed to evaluate the protein expression profile in wound tissues from healthy controls (HC) and DFU. Kyoto Encyclopedia of Genes (KEGG) and Genomes enrichment analysis (GO) was conducted based on differentially expressed proteins (DEPs) to discover the potential pathways associated with DFU. Western blot analysis was used to confirm the probable DFU-related targets. Proteomics analysis discovered 509 DEPs (248 upregulated and 261 downregulated proteins). Go and KEGG further evaluated the DEPs to discover the DFU-related pathways. According to network pharmacology study, three main targets (metalloproteinase 9 (MMP9), Fatty acid-binding protein 5 (FABP5), and integrin subunit alpha M (ITGAM)) play crucial roles in signaling pathways. Staphylococcus aureus infection and leukocyte transendothelial migration pathways significantly enriched in DFU. In addition, it was confirmed that three critical targets were elevated in diabetes mouse wound tissues. The study confirmed the presence of protein alterations in the wound-healing process of DFU mice and may provide fresh insights into the molecular mechanisms driving DFU.
足部溃疡是糖尿病的常见并发症，与糖尿病患者的高发病率和死亡率有关。本研究旨在通过蛋白质组学和网络药理学分析研究糖尿病足溃疡（DFU）的新愈合途径。采用串联质量标签（TMT）标记定量蛋白质组学方法评估健康对照组（HC）和 DFU 创面组织中的蛋白质表达谱。根据差异表达蛋白（DEPs）进行京都基因与基因组百科全书（KEGG）和基因本体论（GO）分析，以发现与 DFU 相关的潜在途径。Western blot 分析用于确认可能的 DFU 相关靶标。蛋白质组学分析发现 509 个 DEP（248 个上调和 261 个下调蛋白）。GO 和 KEGG 进一步评估 DEP 以发现 DFU 相关途径。根据网络药理学研究，三个主要靶标（基质金属蛋白酶 9（MMP9）、脂肪酸结合蛋白 5（FABP5）和整合素亚基α M（ITGAM））在信号通路中发挥关键作用。金黄色葡萄球菌感染和白细胞跨内皮迁移途径在 DFU 中显著富集。此外，还证实了三种关键靶标在糖尿病小鼠创面组织中升高。该研究证实了 DFU 小鼠创面愈合过程中存在蛋白质变化，可能为驱动 DFU 的分子机制提供新的见解。
