Zhang Jixun, Wang Chao, Dong Xinxin
Department of Plastic and Burn Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, People's Republic of China.
Eur J Med Res. 2025 Aug 26;30(1):813. doi: 10.1186/s40001-025-03056-7.
Macrophage polarization plays a crucial role in the processes of inflammation, angiogenesis, and wound healing. N6-methyladenosine (mA) RNA modification has been widely recognized as an abundant modification that regulates RNA expression. This work aimed to investigate the function of mA modified Socs1 in skin wound healing.
A full-thickness skin wounds mouse model was established and treated with Socs1 overexpression. The wound healing process and the histological changes of skin tissues were detected. Ana-1 macrophages were treated with lipopolysaccharide (LPS) to mimic the inflammatory environment during the wound healing process. The macrophage polarization was detected by immunofluorescence staining of specific biomarkers and production of inflammatory factors was measured using ELISA kits. Angiogenesis and fibroblast proliferation and migration were measured by the co-culture system of Ana-1 with dermal microvascular endothelial cells (DMECs) or dermal fibroblasts (DFs). The mA modification of Socs1 mRNA was measured by mA mRNA immunoprecipitation.
Socs1 expression was upregulated during wound healing process and M2 polarization of macrophages. Socs1 overexpression accelerated mouse skin wound healing and enhanced the formation of granulation tissue in wound tissues. Co-culture with Socs1-overexpressed macrophages increased angiogenesis of DMECs and enhanced the viability and migration of DFs. METTL14 regulates Socs1 expression in Ana-1 cells and increased the mA methylation of Socs1 mRNA by recruiting YTHDF1.
Socs1 regulates the M2 macrophages polarization and accelerates wound healing, which is modulated by METTL14-mediated mA modification of Socs1 mRNA through YTHDF1 recruitment in macrophages.
巨噬细胞极化在炎症、血管生成和伤口愈合过程中起关键作用。N6-甲基腺苷（m6A）RNA修饰已被广泛认为是一种调节RNA表达的丰富修饰。本研究旨在探讨m6A修饰的细胞因子信号转导抑制因子1（Socs1）在皮肤伤口愈合中的作用。
建立全层皮肤伤口小鼠模型，并用Socs1过表达进行处理。检测伤口愈合过程及皮肤组织的组织学变化。用脂多糖（LPS）处理Ana-1巨噬细胞，以模拟伤口愈合过程中的炎症环境。通过特异性生物标志物的免疫荧光染色检测巨噬细胞极化，并使用ELISA试剂盒测量炎症因子的产生。通过Ana-1与真皮微血管内皮细胞（DMECs）或真皮成纤维细胞（DFs）的共培养系统测量血管生成、成纤维细胞增殖和迁移。通过m6A mRNA免疫沉淀法检测Socs1 mRNA的m6A修饰。
在伤口愈合过程和巨噬细胞的M2极化过程中，Socs1表达上调。Socs1过表达加速了小鼠皮肤伤口愈合，并增强了伤口组织中肉芽组织的形成。与过表达Socs1的巨噬细胞共培养可增加DMECs的血管生成，并增强DFs的活力和迁移能力。甲基转移酶样蛋白14（METTL14）调节Ana-1细胞中Socs1的表达，并通过招募YTHDF1增加Socs1 mRNA的m6A甲基化。
Socs1调节M2巨噬细胞极化并加速伤口愈合，这是由METTL14通过在巨噬细胞中招募YTHDF1介导的Socs1 mRNA的m6A修饰所调节的。
