After Skin Wounding, Noncoding dsRNA Coordinates Prostaglandins and Wnts to Promote Regeneration.

Autor: Zhu AS; Department of Dermatology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA., Li A; Department of Dermatology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA., Ratliff TS; Department of Dermatology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA., Melsom M; Department of Biology, Johns Hopkins University, Baltimore, Maryland, USA., Garza LA; Department of Dermatology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. Electronic address: LAG@jhmi.edu.
Jazyk: angličtina
Zdroj: The Journal of investigative dermatology [J Invest Dermatol] 2017 Jul; Vol. 137 (7), pp. 1562-1568. Date of Electronic Publication: 2017 Apr 06.
DOI: 10.1016/j.jid.2017.03.023
Abstrakt: In a rare example akin to organogenesis in adult mammals, large wounds in mice lead to de novo morphogenesis of hair follicles. It is still not fully clear what controls this process, known as wound-induced hair neogenesis (WIHN). In other tissues, prostaglandin E 2 is an important effector of regeneration and has been shown to stimulate the Wnt/β-catenin pathway, which in turn is known to control WIHN. Previously, our group has shown that noncoding double-stranded RNA (dsRNA) released during wounding is both necessary and sufficient to stimulate WIHN through toll-like receptor 3. Here, we hypothesized that dsRNA similarly induces the β-catenin pathway through prostaglandin E 2 . We found that WIHN levels correlate closely with Wnt7b production in vivo and that dsRNA potently induces Wnt7b in a manner that requires Ptgs2. The Ptgs2 inhibitor celecoxib reduces dsRNA-induced WIHN and Wnt7b, and exogenous prostaglandin E 2 can rescue WIHN and Wnt7b. Although other Wnts and pathways likely contribute, these results highlight noncoding dsRNA as an upstream coordinator of prostaglandin and Wnt levels in regeneration.
(Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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