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Published on: April 7, 2017
miR-483-3p controls proliferation in wounded epithelial cells
Thomas Bertero1, Cécile Gastaldi, Isabelle Bourget-Ponzio
1INSERM U634, IFR50, Faculté de Médecine, France.
Summary
MicroRNAs (miRNAs) play a role in wound healing. This study reveals that miR-483-3p up-regulation inhibits keratinocyte proliferation and migration, suggesting a novel mechanism for controlling skin repair.
Area of Science:
- Molecular Biology
- Dermatology
- Wound Healing Research
Background:
- Keratinocyte migration and proliferation are crucial for wound healing but the underlying mechanisms, especially involving microRNAs (miRNAs), are not fully understood.
- MicroRNAs are small non-coding RNAs that regulate gene expression and are implicated in various biological processes, including tissue repair.
Purpose of the Study:
- To investigate the role of microRNAs, specifically miR-483-3p, in regulating keratinocyte behavior during wound healing.
- To identify the direct targets of miR-483-3p involved in controlling keratinocyte proliferation and migration.
Main Methods:
- Utilized scratch-injured human keratinocyte cultures and wounded mouse skin models to study miR-483-3p expression.
- Employed videomicroscopy and 5-bromo-2'-uridine incorporation to assess keratinocyte migration and proliferation.
- Performed expression profiling, luciferase reporter assays, Western blot, and siRNA silencing to identify and validate miR-483-3p targets.
Main Results:
- miR-483-3p was found to be up-regulated during wound healing, peaking at the final stage.
- Overexpression of miR-483-3p inhibited keratinocyte migration and proliferation; conversely, anti-miR-483-3p oligonucleotides promoted proliferation.
- Kinase MK2, proliferation marker MKI67, and transcription factor YAP1 were identified as direct targets of miR-483-3p, mediating its effects on keratinocyte growth.
Conclusions:
- miR-483-3p acts as a negative regulator of keratinocyte proliferation and migration during wound healing.
- The down-regulation of MK2, MKI67, and YAP1 by miR-483-3p represents a novel mechanism controlling keratinocyte growth arrest in reepithelialization.
- This finding offers potential therapeutic targets for modulating wound healing processes.
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