After Skin Wounding, Noncoding dsRNA Coordinates Prostaglandins and Wnts to Promote Regeneration.
After Skin Wounding, Noncoding dsRNA Coordinates Prostaglandins and Wnts to Promote Regeneration.
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DOI：
10.1016/j.jid.2017.03.023
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发表时间：
2017-07
期刊：
影响因子：
--
通讯作者：
Garza LA
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文献类型：
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作者：
Zhu AS;Li A;Ratliff TS;Melsom M;Garza LA
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 E2 (PGE2) is an important effector of regeneration and has been shown to stimulate the Wnt/beta-catenin pathway, which in turn is known to control WIHN. Previously, our group has demonstrated that noncoding dsRNA released during wounding is both necessary and sufficient to stimulate WIHN through TLR3. Here, we hypothesize that dsRNA similarly induces the beta-catenin pathway through PGE2. We find that WIHN levels correlate closely to Wnt7b production in vivo, and that dsRNA potently induces Wnt7b in a manner that requires prostaglandin-endoperoxide synthase 2 (Ptgs2). The Ptgs2 inhibitor celecoxib reduces dsRNA-induced WIHN and Wnt7b, and exogenous PGE2 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.
