MiR-181d-5p affects skin wound healing processes via the Ikbkg/NF-κB axis.

The skin, a vital barrier against environmental damage, plays a crucial role in maintaining organismal homeostasis. However, the molecular mechanisms underlying skin wound repair remain incompletely understood, with microRNA regulation potentially serving as a key regulatory component. Utilizing the amphibian-derived cyclic peptide Cy as a molecular probe, we identified the miR-181d-5p/Ikbkg/NF-κB axis as significantly associated with wound healing through small RNA sequencing of early-stage skin injury. Mechanistically, inhibition of miR-181d-5p during the early phase elevated the release of pro-inflammatory cytokines (TNF-α, IL-1β) and enhanced macrophage migration. In vivo, inhibition of miR-181d-5p accelerated full-thickness skin wound healing in mice, confirming its role in promoting the inflammatory phase transition. Collectively, these findings indicate that early suppression of miR-181d-5p activates the Ikbkg/NF-κB signaling pathway, thereby facilitating the transition from the inflammatory to the proliferative phase and accelerating skin repair. Conducted within the regulatory network of ceRNA, the study uncovers the potential of miR-181d-5p as a therapeutic target for wound healing and provides a novel interventional strategy for enhancing skin repair.