Early Induction of NRF-2 Antioxidant Pathway by RHBDF2 Mediates More Rapid Cutaneous Healing in Mice. Mus musculus

Rhomboid family protein RHBDF2, an upstream regulator of the epidermal growth factor (EGF) receptor signaling, has been implicated in cutaneous wound healing. However, the underlying molecular mechanisms are still emerging. Using a gain-of-function mutation in the mouse Rhbdf2 gene (Rhbdf2cub/cub), which shows a regenerative phenotype, we sought to identify the underlying mechanism. Transcriptome analyses were performed to identify early-stage pathways and biological processes that function post-wound healing in Rhbdf2cub/cub and control Rhbdf2+/+ mice. Overall design: Two-mm through-and-through holes were punched into the ears of 4-wk-old Rhbdf2+/+ and Rhbdf2cub/cub female mice and ear pinna tissue was collected at 0h, 15 min, 2h, and 24h post-wounding (three mice per time point). A total of 23 Affymetrix Mouse Gene 1.0 ST Arrays were used for gene expression analysis. For this experiment, pairwise comparisons were used to statistically resolve gene-expression differences between genotype groups at 0h, 15 min, 2h, and 24h using the R/maanova analysis package.Differentially expressed genes were declared at an FDR q-value threshold of 0.05.