Differential expression of tension-sensitive HOX genes in fibroblasts is associated with different scar types

A scar is considered a natural consequence of the wound-healing process. However, the mechanism by which scars form remains unclear. Here, we suggest a new mechanism of wound healing and scar formation that involves the mechanosensitive regulation of HOX genes. RNA-sequencing of fibroblasts from different types of scars revealed differential HOX gene expression. Computational simulations predicted injury-induced tension loss in the skin, and in vitro experiments revealed a negative correlation between tension and fibroblast proliferation. Remarkably, exogenous tensile stress in fibroblasts has been shown to alter HOX gene expression levels in different scar types. Overall, we propose a model for normal wound healing and scar formation and show that successful wound healing requires tensional homeostasis in the skin tissue, which is regulated by tension-sensitive HOX genes.