Oxygenation state as a driver of myofibroblast differentiation and wound contraction: hypoxia impairs wound closure

Myofibroblasts are ubiquitous in the human body and may form from the differentiation of fibroblasts, epithelial cells, endothelial cells, and mononuclear cells, among others. Their clinical significance could be substantial, depending on biomedical context. Myofibroblasts help contract open skin wounds, but they could also be key drivers of fibrosis across numerous tissue systems and support tumor invasiveness. Understanding the molecular events underlying myofibroblast formation is significant for many human diseases. In this issue, Modarressi et al. address the significance of wound tissue hypoxia in impairing wound contraction by compromising myofibroblast formation. They present compelling evidence indicating tissue hypoxia conflicts with wound closure. We are reminded that correcting wound tissue hypoxia is critical for the tissue's response to other therapeutic interventions.