MiR-31 mediates inflammatory signaling to promote re-epithelialization during skin wound healing
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Wound healing is essential for skin repair after injury, and consists of hemostasis, inflammation, re-epithelialization and remodeling phases. Successful re-epithelialization, which relies on proliferation and migration of epidermal keratinocytes, requires reduction in tissue inflammation. Therefore, understanding the molecular mechanism underlying the transition from inflammation to re-epithelialization will help to better understand the principles of wound healing. Currently, the in vivo functions of specific microRNAs in wound healing are not fully understood. We observed that miR-31 expression is strongly induced in wound edge keratinocytes, and is directly regulated by the activity of NF-κB and STAT3 signaling pathways during inflammation phase. We utilized miR-31 loss-of-function mouse models to demonstrate that miR-31 promotes keratinocyte proliferation and migration. Mechanistically, miR-31 activates the RAS/MAPK signaling by directly targeting Rasa1, Spred1, Spred2 and Spry4, which are negative regulators of the RAS/MAPK pathway. Knockdown of these miR-31 targets at least partially rescues the delayed scratch wound re-epithelialization phenotype observed in vitro in miR-31 knockdown keratinocytes. Taken together, these findings identify miR-31 as an important cell-autonomous mediator during the transition from inflammation to re-epithelialization phases of wound healing, suggesting a therapeutic potential for miR-31 in skin injury repair.
Date Issued
2018-10-01
Date Acceptance
2018-03-19
Citation
Journal of Investigative Dermatology, 2018, 138 (10), pp.2253-2263
ISSN
0022-202X
Publisher
Elsevier
Start Page
2253
End Page
2263
Journal / Book Title
Journal of Investigative Dermatology
Volume
138
Issue
10
Copyright Statement
© 2018 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/29605672
PII: S0022-202X(18)31857-8
Subjects
RAS/MAPK
keratinocyte proliferation and migration
miR-31
microRNA
wound healing
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2018-03-30