METTL14-mediated m6A methylation promotes macrophage M2 polarization via YTHDF1-Socs1 axis to accelerate skin wound healing
Year: 2025
Type: article
Abstract: Macrophage polarization plays a crucial role in the processes of inflammation, angiogenesis, and wound healing. N6-methyladenosine (m 6 A) RNA modification has been widely recognized as an abundant modification that regulates RNA expression. This work aimed to investigate the function of m 6 A 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 m 6 A modification of Socs1 mRNA was measured by m 6 A 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 m 6 A methylation of Socs1 mRNA by recruiting YTHDF1. Socs1 regulates the M2 macrophages polarization and accelerates wound healing, which is modulated by METTL14-mediated m 6 A modification of Socs1 mRNA through YTHDF1 recruitment in macrophages.
Authors: Jixun Zhang, Chao Wang, Xinxin Dong
Institutions: Shandong University, Second Hospital of Shandong University
Language: English
Topic: Wound Healing and Treatments
Subfield: Rehabilitation
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,190
OpenAlex ID: W4413682727