Skin wound healing, a complex biological process that is critical for restoring barrier function, remains a significant clinical challenge. The aim of this study was to investigate the role of meteorin-like (Metrnl) in acute cutaneous wound repair and the underlying mechanisms involved. In a rat full-thickness skin wound model, Metrnl expression was dynamically upregulated, peaking on Day 4 after injury. Topical application of recombinant Metrnl protein (rMet) significantly accelerated wound closure and improved healing quality, as evidenced by increased re-epithelialization, collagen deposition, and epithelial‒mesenchymal transition (EMT) marker expression (E-cadherin downregulation; vimentin and N-cadherin upregulation). In vitro, rMet promoted the proliferation and migration of primary rat epidermal keratinocytes (REKs). This finding was further validated by Metrnl overexpression and knockdown. Transcriptomic analysis of wounded rat skin and rMet-stimulated REKs revealed that EMT-related differentially expressed genes (DEGs) were enriched in the PI3K–Akt pathway, among other pathways. Mechanistically, Metrnl activated the c-Kit/Akt/FoxO3a axis in a time-dependent manner; rMet induced the phosphorylation of c-Kit, Akt, and FoxO3a, triggering FoxO3a nuclear export. Inhibitor experiments confirmed that FoxO3a translocation depended on c-Kit/Akt activation. Furthermore, FoxO3a activated Smad7 transcription, whereas Metrnl antagonized this effect, thereby regulating EMT through Smad7 and EMT-related molecules. In conclusion, Metrnl accelerates wound healing by promoting keratinocyte proliferation and migration via the c-Kit/Akt/FoxO3a axis, modulating Smad7 expression and EMT progression. These findings highlight Metrnl as a potential therapeutic target for increasing wound repair.
DOI: 10.1155/dth/5524084
