CD31-derived ICP peptide enhances epidermal and dermal regeneration in murine cutaneous wounds

Chronic wounds affect millions globally, yet current therapies often fail to coordinate the complex interplay of epithelial, dermal, and immune repair processes, leading to suboptimal healing outcomes. This gap highlights the need for novel agents that can orchestrate these diverse cellular activities. The cytoplasmic domain of CD31 contains an immunoreceptor tyrosine-based inhibitory motif (ITIM), a signaling motif known to modulate cellular activity. Peptides derived from such motifs, like ICP, are being explored for their potential to coordinate complex repair processes in cutaneous wound repair.

The study evaluated the effects of ICP (a 16-amino acid immunoreceptor tyrosine-based inhibitory motif-containing peptide) on proliferation, migration, cell-cycle progression, intracellular localization, and ERK signaling in HaCaT keratinocytes and Hs27 fibroblasts. In vivo efficacy was assessed in murine full-thickness dorsal and ear wounds. Animals received either local or systemic ICP administration. Primary endpoints included wound closure rates, histological architecture, and the expression of various cellular markers, analyzed at days 8 and 14 post-wounding.

ICP significantly enhanced both keratinocyte and fibroblast proliferation and migration, evidenced by increased Ki-67 expression and promotion of G2/M cell cycle progression. The peptide also induced ERK phosphorylation and internalized efficiently into both cell types, showing diffuse cytoplasmic localization. In murine models, local or systemic ICP administration consistently accelerated wound closure. Histological analysis revealed a reduction in epithelial gaps and diminished granulation tissue, alongside improved overall tissue organization.

ICP-treated wounds exhibited increased keratinocyte proliferation without aberrant keratin10 expression, significantly diminished CD11b+ myeloid infiltration, and elevated keratin15 and LGR5 expression, indicating activation of epithelial and follicular stem/progenitor populations.