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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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Aav ; Fascia ; Fibroblasts ; Scar ; Skin ; Wound ; P120; Mesenchymal Stem-cells; Gene-transfer; Vector; Catenin; Transduction; Motility; Wounds
ISSN (print) / ISBN 0022-202X
e-ISSN 1523-1747
Journal Journal of Investigative Dermatology, The
Quellenangaben Volume: 143, Issue: 5, Pages: , Article Number: 854-863.e4 Supplement: ,
Publisher Elsevier
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Regenerative Biology (IRBM)
Institute of Asthma and Allergy Prevention (IAP)
Grants LEO Foundation
Else Kroner-Fresenius-Stiftung
European Research Council Consolidator Grant
Fritz Thyssen Stiftung
German Research Foundation
Human Frontier Science Program Career Development Award