In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37

This study provided detailed evidence of the molecular mechanisms by which the antimicrobial peptide LL-37 promotes wound healing, combining in vitro experiments with in vivo animal models. The researchers used human keratinocytes, scratch wound assays, and humanized skin models in mice.

In vitro, LL-37 significantly stimulated keratinocyte migration in wound closure assays, without substantially affecting cell proliferation. This migratory response was accompanied by striking phenotypic changes, including reorganization of the actin cytoskeleton, lamellipodia formation, and a shift to a migratory phenotype typical of activated keratinocytes.

The mechanism of action involves transactivation of the EGF receptor (EGFR) by LL-37, triggering the STAT3 signaling pathway that is essential for epithelial migration during wound healing. Pharmacological inhibition of EGFR significantly blocked the pro-migratory effects of LL-37, confirming this pathway as a central mediator.

In the in vivo models of human skin regenerated on immunodeficient mice, topical application of LL-37 accelerated wound re-epithelialization. These results complement the findings of Heilborn et al. (2003) and reinforce the concept that LL-37 is more than an antimicrobial peptide — it is a true tissue repair mediator with direct therapeutic potential for chronic wounds.