Full-Length Laminin-332 Promotes Integrin α3β1-Dependent Cutaneous Wound Closure in a Murine Model.

Background

Cutaneous wound repair requires rapid re-epithelialization to restore barrier function and protect against infection. This process depends on coordinated keratinocyte migration and proliferation, and its impairment contributes to slow wound healing and increased healthcare burden. Current extracellular matrix (ECM)-based therapies largely target the dermis, while the therapeutic potential of epidermal basement membrane (BM) components remains underexplored. BM protein laminin-332 (LN332) is upregulated after injury and promotes keratinocyte migration. It functions as a key ligand for integrin α3β1, which is highly expressed by basal keratinocytes and further induced after wounding.

Objectives

We aimed to investigate whether topical application of recombinant full-length LN332 could enhance wound repair in vivo and we examined the requirement for integrin α3β1 in this process.

Methods

We used a full-thickness murine wound model with topical treatments of LN332 or a vehicle control, combined with a murine model of epidermis-specific integrin α3β1 deletion.

Results

LN332 treatment accelerates re-epithelialization, and α3β1 is required for this effect. In addition to its direct effects on re-epithelialization, exogenous LN332 modulates several α3β1-dependent genes, including nerve growth factor (NGF). Our current study identifies NGF as an α3β1-dependent and LN332-responsive mediator of keratinocyte migration during wound healing.

Conclusions

These findings identify the LN332-integrin α3β1-NGF axis as a promising therapeutic target for promoting re-epithelialization and improving healing outcomes.