Mao Haoran, Jiang Xiao, Liang Jiaji, Zhang Lei, Yang Zixian, Chen Zhijing, Qiao Jinlong, An Xifeng, Li Xuangu, Xie Guanghui, Liu Hong-Wei, Xiao Liling
Department of Plastic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, Guangdong, People's Republic of China.
Key Laboratory of Regenerative Medicine, Innovative Technology Research Institute of Tissue Repair and Regeneration, Ministry of Education, Guangzhou, 510630, Guangdong, People's Republic of China.
Sci Rep. 2025 May 12;15(1):16457. doi: 10.1038/s41598-025-99128-z.
Keratinocytes, the most important cell type constituting the epidermis, migrate to restore the epithelial barrier during wound healing and are a crucial step in wound healing. This study utilized bioinformatics analysis of comprehensive expression datasets of aberrantly expressed genes in wound healing to identify the abnormal expression of the critical transcription factor Fos-like antigen-1 (FOSL1), which is involved in various diseases. Currently, there is limited research on the role of FOSL1 in wound healing, and its molecular mechanisms remain unclear. This study explores the role and regulatory mechanisms of FOSL1 in the wound-healing process. A comprehensive expression dataset of abnormal genes in wound repair was constructed by bioinformatics analysis. Mouse trauma models and mouse wound splint models were constructed to verify the role of FOSL1 in vivo. Real-time quantitative polymerase chain reaction (qRT-PCR), immunoblot, immunofluorescence staining, and HE staining were used to confirm the analysis, and FOSL1 was used as the target in the wound healing process. At the cellular level, using 5'-ethynyl-2'-deoxyuridine (EdU) assay, Transwell assay, Migration assay, western blotting and immunofluorescence, FOSL1 promoted the molecular mechanism of wound repair by regulating the proliferation and migration of keratinocytes through IL-17 signaling pathway. Bioinformatics analysis revealed differential expression of FOSL1 during wound healing. In the mouse back wound model, qRT-PCR, western blotting (WB), and immunofluorescence staining showed significant upregulation of FOSL1 and IL-17 expression during wound tissue healing, indicating a close association between FOSL1 and mouse wound healing. In the mouse wound splinting model, subcutaneous injection of recombinant FOSL1 protein contributed to wound surface healing. Overexpression of FOSL1 in HaCaT cells promoted their proliferation and migration abilities. When IL-17 inhibitor was added to HaCaT cells, both FOSL1 overexpression and knockdown inhibited the proliferation and migration abilities of HaCaT cells. Thus, this study confirms that FOSL1 promotes keratinocyte proliferation and migration through the IL-17 signaling pathway, facilitating wound healing in epidermal wound repair. The results of this study indicate that FOSL1 plays a key role in epidermal wound healing, and elucidate a new molecular mechanism by which FOSL1 promotes keratinocyte proliferation and migration through IL-17 signaling pathway in epidermal wound repair, thereby promoting wound healing.
角质形成细胞是构成表皮的最重要细胞类型，在伤口愈合过程中迁移以恢复上皮屏障，是伤口愈合的关键步骤。本研究利用伤口愈合中异常表达基因的综合表达数据集进行生物信息学分析，以鉴定关键转录因子Fos样抗原1（FOSL1）的异常表达，FOSL1与多种疾病有关。目前，关于FOSL1在伤口愈合中的作用研究有限，其分子机制尚不清楚。本研究探讨FOSL1在伤口愈合过程中的作用及其调控机制。通过生物信息学分析构建了伤口修复中异常基因的综合表达数据集。构建小鼠创伤模型和小鼠伤口夹板模型以验证FOSL1在体内的作用。使用实时定量聚合酶链反应（qRT-PCR）、免疫印迹、免疫荧光染色和HE染色来证实分析结果，并将FOSL1作为伤口愈合过程中的靶点。在细胞水平上，使用5'-乙炔基-2'-脱氧尿苷（EdU）检测、Transwell检测、迁移检测、蛋白质免疫印迹和免疫荧光，FOSL1通过IL-17信号通路调节角质形成细胞的增殖和迁移，从而促进伤口修复的分子机制。生物信息学分析揭示了伤口愈合过程中FOSL1的差异表达。在小鼠背部伤口模型中，qRT-PCR、蛋白质免疫印迹（WB）和免疫荧光染色显示伤口组织愈合过程中FOSL1和IL-17表达显著上调，表明FOSL1与小鼠伤口愈合密切相关。在小鼠伤口夹板模型中，皮下注射重组FOSL1蛋白有助于伤口表面愈合。FOSL1在HaCaT细胞中的过表达促进了它们的增殖和迁移能力。当向HaCaT细胞中加入IL-17抑制剂时，FOSL1的过表达和敲低均抑制了HaCaT细胞的增殖和迁移能力。因此，本研究证实FOSL1通过IL-17信号通路促进角质形成细胞的增殖和迁移，促进表皮伤口修复中的伤口愈合。本研究结果表明FOSL1在表皮伤口愈合中起关键作用，并阐明了一种新的分子机制，即FOSL1在表皮伤口修复中通过IL-17信号通路促进角质形成细胞的增殖和迁移，从而促进伤口愈合。
