Differential expression of tension-sensitiveHOXgenes in fibroblasts is associated with different scar types

Abstract

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.

Comparative computational analysis to distinguish mesenchymal stem cells from fibroblasts

“…HOXA9 and HOXC10, for example, were reported to be upregulated in highly proliferating fibroblasts, finally forming hypertrophic scars (53). Similar to the role of HOXA9 in regulating fibroblast proliferation, HOXB9 overexpression was shown to be involved in excessive proliferation, finally facilitating hypertrophic scar formation (54).…”