Therapeutic Silencing of p120 in Fascia Fibroblasts Ameliorates Tissue Repair

Deep skin wounds rapidly heal by mobilizing extracellular matrix and cells from the fascia, deep beneath the dermal layer of the skin, to form scars. Despite wounds being an extensively studied area and an unmet clinical need, the biochemistry driving this patch-like repair remains obscure. Lacking also are efficacious therapeutic means to modulate scar formation in vivo. In this study, we identify a central role for p120 in mediating fascia mobilization and wound repair. Injury triggers p120 expression, largely within engrailed-1 lineage-positive fi-broblasts of the fascia that exhibit a supracellular organization. Using adeno-associated virus-mediated gene silencing, we show that p120 establishes the supracellular organization of fascia engrailed-1 lineage-positive fibroblasts, without which fascia mobilization is impaired. Gene silencing of p120 in fascia fibroblasts disen-tangles their supracellular organization, reducing the transfer of fascial cells and extracellular matrix into wounds and augmenting wound healing. Our findings place p120 as essential for fascia mobilization, opening, to our knowledge, a previously unreported therapeutic avenue for targeted intervention in the treatment of a variety of skin scar conditions.

Automated summary

Deep skin wounds heal by mobilizing cells and extracellular matrix from the fascia, but the biochemistry and therapeutic means to modulate scar formation are not well understood. This study identifies p120 as a key mediator of fascia mobilization and wound repair. Gene silencing of p120 disrupts the supracellular organization of fascia fibroblasts, reducing cell and matrix transfer into wounds and enhancing wound healing. These findings suggest p120 as a potential therapeutic target for the treatment of skin scar conditions.