Peng Yinbo, Sheng Juxiang, Liu Tiantian, He Ruizhe, Xu Peng
Department of Burns and Plastic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201900, China.
Department of Plastic Surgery and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201900, China.
Arch Dermatol Res. 2025 Apr 19;317(1):719. doi: 10.1007/s00403-025-04140-y.
Wound healing (WH) poses a significant socio-economic burden due to its high incidence and recurrence rates. Iron overload (IO) could be a factor leading to delayed WH. This study thus analyzed IO-related genes (IORGs) in WH, offering possibilities for developing new therapeutic strategies. Differential gene expression (DEGs) analysis was conducted between the WH group and intact skin (IS) group, intersected with IORGs to obtain differentially expressed IORGs (DE-IORGs). Functional enrichment analysis and potential drug screening were performed on DE-IORGs. A protein-protein interaction (PPI) network of DE-IORGs was constructed, and hub genes were identified using CytoHubba and MCODE methods. ROC curves of hub genes were plotted, and their expression levels in WH and IS groups as well as inter-gene correlations were analyzed. Additionally, immune infiltration variances in WH and IS groups, along with miRNA and TFs of hub genes, were examined. Finally, the effect of EGFR on skin wound healing was verified by scratch healing assay. 39 DE-IORGs were predominantly enriched in signaling pathways like HIF-1 signaling pathway and Th17 cell differentiation. Potential drugs for treating WH (e.g., felbamate, SA-94315, GANT-58, rucaparib) were identified. Three hub genes related to IO in WH were pinpointed (HIF1A, CDKN2A, EGFR) with diagnostic value. Immune infiltration analysis showed higher levels of immune cells like endothelial cells and macrophages in the WH group. Additionally, 55 miRNAs (e.g., hsa-mir-200a-3p, hsa-mir-218-5p) and 2 TFs (L3MBTL2, ZNF76) regulating the three hub genes were predicted. Cell experiments showed that EGFR could promote skin wound healing. The study suggested HIF1A, CDKN2A, and EGFR as potential diagnostic biomarkers for effective WH diagnosis, offering new insights into identifying potenti1al therapeutic targets for WH treatment.
伤口愈合（WH）因其高发病率和复发率而带来巨大的社会经济负担。铁过载（IO）可能是导致伤口愈合延迟的一个因素。因此，本研究分析了伤口愈合中与铁过载相关的基因（IORGs），为开发新的治疗策略提供了可能性。在伤口愈合组和完整皮肤（IS）组之间进行差异基因表达（DEGs）分析，并与IORGs相交以获得差异表达的IORGs（DE-IORGs）。对DE-IORGs进行功能富集分析和潜在药物筛选。构建了DE-IORGs的蛋白质-蛋白质相互作用（PPI）网络，并使用CytoHubba和MCODE方法鉴定了枢纽基因。绘制了枢纽基因的ROC曲线，并分析了它们在伤口愈合组和完整皮肤组中的表达水平以及基因间的相关性。此外，还检查了伤口愈合组和完整皮肤组中的免疫浸润差异，以及枢纽基因的miRNA和转录因子。最后，通过划痕愈合试验验证了表皮生长因子受体（EGFR）对皮肤伤口愈合的作用。39个DE-IORGs主要富集在缺氧诱导因子-1（HIF-1）信号通路和辅助性T细胞17（Th17）细胞分化等信号通路中。确定了用于治疗伤口愈合的潜在药物（如非氨酯、SA-94315、GANT-58、鲁卡帕尼）。确定了伤口愈合中与铁过载相关的三个具有诊断价值的枢纽基因（HIF1A、CDKN2A、EGFR）。免疫浸润分析显示，伤口愈合组中内皮细胞和巨噬细胞等免疫细胞水平较高。此外，预测了调控这三个枢纽基因的55个miRNA（如hsa-mir-200a-3p、hsa-mir-218-5p）和2个转录因子（L3MBTL2、ZNF76）。细胞实验表明，EGFR可以促进皮肤伤口愈合。该研究表明，HIF1A、CDKN2A和EGFR作为有效的伤口愈合诊断的潜在生物标志物，为确定伤口愈合治疗的潜在靶点提供了新的见解。
