title: After Skin Wounding, Noncoding dsRNA Coordinates Prostaglandins and Wnts to Promote Regeneration.
abstract: 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 E2is 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 E2. 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 E2can 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.
authors.affiliation: Department of Dermatology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors.forename: Amadeus S
authors.initials: AS
authors.lastname: Zhu
authors.affiliation: Department of Dermatology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Dermatology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors.forename: Tabetha S
authors.initials: TS
authors.lastname: Ratliff
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Martha
authors.initials: M
authors.lastname: Melsom
authors.affiliation: Department of Dermatology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. Electronic address: LAG@jhmi.edu.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Garza
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D015151:Immunoblotting; D008810:Mice, Inbred C57BL; D011453:Prostaglandins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D012330:RNA, Double-Stranded / Q000235:genetics*; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D051153:Wnt Proteins / Q000096:biosynthesis / Q000235:genetics*; D060449:Wnt Signaling Pathway; D014945:Wound Healing / Q000235:genetics; D014947:Wounds and Injuries / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D011453:Prostaglandins; D011518:Proto-Oncogene Proteins; D012330:RNA, Double-Stranded; D051153:Wnt Proteins; C095937:Wnt7b protein, mouse