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 fibroblasts 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 disentangles 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.
Abbreviations:
AAV (adeno-associated virus), ECM (extracellular matrix), PIV (particle image velocimetry), shRNA (short hairpin RNA)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: November 25, 2022
Accepted:
October 31,
2022
Received in revised form:
October 22,
2022
Received:
June 20,
2022
accepted manuscript published online XXX; corrected proof published online XXXPublication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology.
