mir-182-5p regulates all three phases of inflammation, proliferation, and remodeling during cutaneous wound healing

Area of Science:

• Molecular Biology
• Dermatology
• Wound Healing Research

Background:

• MicroRNAs (miRNAs) are key regulators of biological processes, including wound healing and scar formation.
• The precise roles of specific miRNAs in cutaneous wound repair and scarification remain incompletely understood.
• Abnormalities in wound healing processes frequently lead to scar development, posing clinical challenges.

Purpose of the Study:

• To investigate the expression patterns of candidate microRNAs in cutaneous wounds with normal repair versus hypertrophic scarring.
• To elucidate the functional role of differentially expressed microRNAs, particularly miR-182-5p, in cellular processes relevant to wound healing.
• To identify potential gene targets of miR-182-5p involved in wound repair and scar pathogenesis.

Main Methods:

• Analysis of microRNA expression in patient-derived cutaneous wound biopsies across different healing phases (inflammation, proliferation, remodeling).
• Quantitative real-time PCR (qRT-PCR) for microRNA and gene expression analysis.
• In vitro assays including cell cycle, scratch, and flow cytometry to assess cell proliferation, migration, and protein expression (TGF-β, αSMA, collagen-I).
• Bioinformatic analysis using the Enrichr tool for target gene prediction.

Main Results:

• Five microRNAs (miR-16-5p, miR-152-3p, miR-125b-5p, miR-34c-5p, and miR-182-5p) showed differential expression between scarring and non-scarring wounds.
• miR-182-5p promoted keratinocyte proliferation and angiogenesis, induced RELA expression, and enhanced fibroblast proliferation, migration, and collagen-1 expression.
• miR-182-5p inhibited keratinocyte migration and led to TGF-β3 overexpression during inflammation, suggesting a role in scar development.
• FoxO1 and FoxO3 were identified as potential targets of miR-182-5p.

Conclusions:

• miR-182-5p exhibits distinct expression profiles in scarring versus normal cutaneous wounds.
• Dysregulated miR-182-5p impacts key cellular behaviors in wound healing, including keratinocyte and fibroblast activity, angiogenesis, and extracellular matrix production.
• Aberrant miR-182-5p expression may disrupt the normal progression of wound healing phases, contributing to scar formation.