Wuguchong Bioactive Peptides Promote Wound Healing via Hedgehog Pathway‑Mediated Fibroblast Modulation.

Abstract

The skin undertakes multiple critical physiological functions, including barrier protection and thermoregulation. However, chronic nonhealing ulcers have emerged as a major clinical challenge. In wound repair, skin healing is a highly coordinated, time-sequential process wherein fibroblasts-key dermal cells-play irreplaceable roles in proliferation, migration, differentiation, and extracellular matrix (ECM) synthesis. When external environmental factors induce fibroblast dysfunction, this can lead to impaired epithelialization, thereby resulting in persistent wound nonclosure, which may represent a key mechanism underlying the pathogenesis of this condition. Yet current clinical treatments (debridement, anti-infection, negative pressure drainage, and growth factors) fail to resolve this, with high recurrence and poorly understood molecular mechanisms. To this end, we identified in this study a low‑molecular‑weight bioactive peptide (< 10 kDa) originating from Wuguchong (JY), which is capable of specifically regulating fibroblasts in the wound microenvironment. By modulating the Hedgehog (Hh) signaling pathway, this peptide restores fibroblast function, thereby promoting wound healing and effectively ameliorating the challenge of impaired wound repair. This study not only offers promise for the development of new drugs for treating ulcers, but also provides novel insights and strategies for cell‑based therapies targeting other types of wound healing.