High-glucose environment impairs keratinocyte migration and proliferation through the ROS/Akt/ETV4 signaling pathway
Impaired diabetic wound healing compromises patient quality of life, with keratinocytes playing a pivotal role in the wound repair process. This in vitro study investigated the role of ETS variant transcription factor 4 (ETV4) in keratinocyte migration/proliferation in high glucose (HG) environments to assess whether ETV4-mediated signaling is involved in dysfunctional wound repair. Western blotting showed that ETV4 expression was downregulated in human keratinocytes cultured in HG. ETV4 knockdown using small interfering RNA suppressed keratinocyte migration/proliferation. Intervention with the reactive oxygen species (ROS) scavenger tempol or the Akt activator SC79 restored ETV4 expression and rescued impaired migration/proliferation. Tempol also restored Akt phosphorylation levels. Matrix metalloproteinase-14 (MMP14) was identified in transcriptome sequencing/bioinformatic analyses as a downstream target of ETV4. HG-suppressed MMP14 expression was reversed by tempol or SC79. Specific inhibition of MMP14 attenuated keratinocyte migration/proliferation in HG. This study reveals a critical role for the ROS/Akt/ETV4/MMP14 signaling axis in HG-induced keratinocyte dysfunction, suggesting potential therapeutic targets for diabetic wound healing. Overall design: This dataset contains transcriptomic profiles of immortalized human keratinocytes (HaCaT) cultured under high glucose conditions following ETV4 knockdown. RNA sequencing was performed using the Illumina platform to investigate how ETV4 suppression modulates gene expression in a diabetic-like microenvironment.The experimental design compared two groups: high glucose control (HG) and ETV4-knockdown under high glucose (HG+siETV4).