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| Status |
Public on Nov 18, 2021 |
| Title |
In vivo gene signature of re-epithelialized tissue post-wounding from wildtype or Rnasel KO mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Mammalian injury responses are characterized by fibrosis and scarring rather than the functional regeneration observed in other phyla. Limited regenerative capacity in mammals could reflect a loss of pro-regeneration programs or active suppression by genes functioning akin to tumor suppressors. To uncover programs governing regeneration in mammals, we investigated Wound Induced Hair Neogenesis (WIHN), a rare example of regeneration in adult mammals1,2. Through comprehensive screening of transcripts associated with both WIHN and human facial rejuvenation after laser treatment, we found the endoribonuclease RNase L to be a powerful suppressor of regeneration. Rnasel-/- mice exhibit remarkable regenerative capacity and accelerated wound healing following injury through the production of IL-36α. Consistent with the known role of RNase L to stimulate caspase-1 signaling, we find that pharmacologic inhibition of caspases promotes regeneration in an IL-36-dependent manner. These responses are not limited to skin but occur following intestinal injury as well, suggesting that suppression of regeneration is a general characteristic of mammalian wound healing. Taken together, this work suggests a therapeutic strategy to uncover latent regenerative capacity and promote functional response to injury.
Biopsies of re-epithelialized tissue were recovered from wild-type or Rnasel KO mice approximately 10 days after wounding. Total RNA was extracted and sent for microarray analysis.
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| Overall design |
Deep tissue wounds of 1.25cm^2 were performed on wild-type or Rnasel KO mice. After 10 days the scab detached (SD0), signifying re-epithelialization. SD0 tissue was surgically removed and total RNA was extracted and submitted for microarray analysis. A single KO sample was compared to a single WT sample.
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| Contributor(s) |
Garza L |
| Citation(s) |
34623736 |
| Submission date |
Dec 29, 2020 |
| Last update date |
Nov 19, 2021 |
| 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) |
| GPL23038 |
[Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA688486 |
