Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 138, Issue 10, Pages 2253-2263Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jid.2018.03.1521
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Funding
- National Natural Science Foundation of China [81572614, 31271584]
- Beijing Nature Foundation Grant [5162018]
- Major Project for Cultivation Technology [2016ZX08008001, 2014ZX08008001]
- Basic Research Program [2015QC0104, 2015TC041, 2016SY001, 2016QC086]
- SKLB Open Grant [2018SKLB6-10]
- Pew Charitable Trust grant
- NIH [R01-AR067273, R01-AR069653]
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR067273, R01AR069653] Funding Source: NIH RePORTER
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Wound healing is essential for skin repair after injury, and it consists of hemostasis, inflammation, re-epithelialization, and remodeling phases. Successful re-epithelialization, which relies on proliferation and migration of epidermal keratinocytes, requires a 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-kappa B and signal transducer and activator of transcription 3 signaling pathways during the inflammation phase. We used miR-31 loss-of-function mouse models to demonstrate that miR-31 promotes keratinocyte proliferation and migration. Mechanistically, miR-31 activates the Ras/mitogen-activated protein kinase signaling by directly targeting Rasa1, Spred1, Spred2, and Spry4, which are negative regulators of the Ras/mitogen-activated protein kinase 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.
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