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Status |
Public on Apr 17, 2017 |
Title |
Gene expression in normal human epidermal keratinocytes treated with poly(I:C) |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
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. These results highlight noncoding dsRNA as a novel upstream coordinator of prostaglandin and Wnt levels in regeneration. We used microarrays to identify the human keratinocyte genes most upregulated or downregulated by poly(I:C)
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Overall design |
Normal human epidermal keratinocytes were cultured in the presence or absence of poly(I:C) as described below. Total RNA was extracted and sent for microarray analysis.
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Contributor(s) |
Zhu AS, Garza LA |
Citation(s) |
28392344 |
NIH grant(s) |
Grant ID |
Grant title |
Affiliation |
Name |
R01 AR068280 |
Towards the clinical testing of dsRNA to promote wound induced hair neogenesis |
JOHNS HOPKINS UNIVERSITY |
Luis Andres Garza |
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Submission date |
Dec 20, 2016 |
Last update date |
Aug 23, 2018 |
Contact name |
Luis Andres Garza |
E-mail(s) |
LAG@jhmi.edu
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Phone |
410-955-8662
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Organization name |
Johns Hopkins School of Medicine
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Department |
Dermatology
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Lab |
Garza lab
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Street address |
1550 Orleans St. Suite 204 CRBII Koch
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City |
Baltimore |
State/province |
MD |
ZIP/Postal code |
21287 |
Country |
USA |
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Platforms (1) |
GPL15207 |
[PrimeView] Affymetrix Human Gene Expression Array |
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Samples (2) |
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Relations |
BioProject |
PRJNA358226 |