eIF6 modulates skin wound healing by upregulating keratin 6B

Area of Science:

• Molecular Biology
• Cell Biology
• Dermatology

Background:

• Eukaryotic translation initiation factor 6 (eIF6) is vital for ribosome biogenesis and protein translation.
• Its role in wound healing and epithelialization remains largely uncharacterized.
• eIF6 is implicated in hypertrophic scar formation.

Purpose of the Study:

• To investigate the role of eIF6 in the process of epithelialization during wound healing.
• To elucidate the molecular mechanisms by which eIF6 influences re-epithelialization.

Main Methods:

• Utilized genetically modified mice with eIF6 knockdown (eIF6+/-) and keratinocyte-specific knockout (eIF6f/+; Krt5-Cre+).
• Employed RNA sequencing (RNA-seq), Western immunoblotting, and immunofluorescence staining to analyze protein expression.
• Investigated the effect of eIF6 knockdown in HaCaT keratinocyte cell lines.

Main Results:

• eIF6 levels negatively correlated with wound healing progression.
• eIF6 knockdown or ablation in mice and keratinocytes accelerated re-epithelialization.
• Upregulation of keratin 6B (KRT6B) and enhanced keratinocyte proliferation were observed upon eIF6 reduction.

Conclusions:

• Downregulation of eIF6 promotes accelerated epithelialization during wound healing.
• This effect is mediated by increased KRT6B expression and enhanced keratinocyte proliferation.
• eIF6 represents a potential novel therapeutic target for regulating re-epithelialization.