PuSH - Publication Server of Helmholtz Zentrum München: Therapeutic silencing of p120 in fascia fibroblasts ameliorate tissue repair.

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Rajendran, V. ; Ramesh, P. ; Dai, R. ; Kalgudde Gopal, S. ; Ye, H. ; Machens, H.G.* ; Adler, H. ; Jiang, D. ; Rinkevich, Y.

Therapeutic silencing of p120 in fascia fibroblasts ameliorate tissue repair.

J. Invest. Dermatol. 143:854-863.e4 (2022)

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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. Here, 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 (EPFs) of the fascia that exhibit a supra-cellular organization. Using adeno-associated virus (AAV) mediated gene silencing, we show that p120 establishes the supracellular organization of fascia EPFs, 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 augments wound healing. Our findings place p120 as essential for fascia mobilization, opening a new therapeutic avenue for targeted intervention in the treatment of a variety of skin scar conditions.

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