Sun Zhen, Qin Yonghong, Zhang Xuanfen
Department of Plastic Surgery, Second Hospital and Clinical Medical School, Lanzhou University, Lanzhou, China.
Front Mol Biosci. 2025 Jan 6;11:1490745. doi: 10.3389/fmolb.2024.1490745. eCollection 2024.
Keloids are a common skin disorder characterized by excessive fibrous tissue proliferation, which can significantly impact patients' health. Ferroptosis, a form of regulated cell death, plays a crucial role in the development of fibrosis; however, its role in the mechanisms of keloid formation remains poorly understood.
This study aimed to identify key genes associated with ferroptosis in keloid formation. Data from the NCBI GEO database, including GSE145725, GSE7890, and GSE44270, were analyzed, comprising a total of 24 keloid and 17 normal skin samples. Additionally, single-cell data from GSE181316, which included 8 samples with complete expression profiles, were also evaluated. Differentially expressed genes were identified, and ferroptosis-related genes were extracted from the GeneCards database. LASSO regression was used to select key genes associated with keloids. Validation was performed using qRT-PCR and Western blot (WB) analysis on tissue samples from five keloid and five normal skin biopsies.
A total of 471 differentially expressed genes were identified in the GSE145725 dataset, including 225 upregulated and 246 downregulated genes. Five ferroptosis-related genes were selected through gene intersection and LASSO regression. Two of these genes were upregulated, while three were downregulated in keloid tissue. Further analysis through GSEA pathway enrichment, GSVA gene set variation, immune cell infiltration analysis, and single-cell sequencing revealed that these genes were primarily involved in the fibrotic process. The qRT-PCR and WB results confirmed the expression patterns of these genes.
This study provides novel insights into the molecular mechanisms of ferroptosis in keloid formation. The identified ferroptosis-related genes could serve as potential biomarkers or therapeutic targets for treating keloids.
瘢痕疙瘩是一种常见的皮肤疾病，其特征在于纤维组织过度增生，这会对患者健康产生重大影响。铁死亡是一种程序性细胞死亡形式，在纤维化发展中起关键作用；然而，其在瘢痕疙瘩形成机制中的作用仍知之甚少。
本研究旨在识别与瘢痕疙瘩形成中铁死亡相关的关键基因。分析了来自NCBI GEO数据库的数据，包括GSE145725、GSE7890和GSE44270，共包含24个瘢痕疙瘩样本和17个正常皮肤样本。此外，还评估了来自GSE181316的单细胞数据，其中包括8个具有完整表达谱的样本。识别差异表达基因，并从GeneCards数据库中提取铁死亡相关基因。使用LASSO回归选择与瘢痕疙瘩相关的关键基因。对来自五例瘢痕疙瘩和五例正常皮肤活检组织样本进行qRT-PCR和蛋白质免疫印迹（WB）分析以进行验证。
在GSE145725数据集中共识别出471个差异表达基因，其中225个上调基因和246个下调基因。通过基因交集和LASSO回归选择了五个铁死亡相关基因。其中两个基因在瘢痕疙瘩组织中上调，而三个基因下调。通过基因集富集分析（GSEA）、基因集变异分析（GSVA）、免疫细胞浸润分析和单细胞测序的进一步分析表明，这些基因主要参与纤维化过程。qRT-PCR和WB结果证实了这些基因的表达模式。
本研究为瘢痕疙瘩形成中铁死亡的分子机制提供了新见解。所识别的铁死亡相关基因可作为治疗瘢痕疙瘩的潜在生物标志物或治疗靶点。
