YAP/TAZ Drive Agrin-Matrix Metalloproteinase 12-Mediated Diabetic Skin Wound Healing.

Macroscopic loss of extracellular matrix can lead to chronic defects in skin wound healing, but supplementation of extracellular matrix holds promise for facilitating wound closure, particularly in diabetic wound healing. We recently showed that the extracellular matrix proteoglycan agrin accelerates cutaneous wound healing by improving mechanoperception of migrating keratinocytes and allowing them to respond to mechanical stresses through matrix metalloproteinase 12 (MMP12). RNA-sequencing analysis revealed that in addition to a disorganized extracellular matrix, agrin-depleted skin cells have impaired YAP/TAZ transcriptional outcomes, leading us to hypothesize that YAP/TAZ, as central mechanosensors, drive the functionality of agrin-MMP12 signaling during cutaneous wound repair.

Agrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing.

An orchestrated wound healing program drives skin repair via collective epidermal cell proliferation and migration. However, the molecular determinants of the tissue microenvironment supporting wound healing remain poorly understood. Herein we discover that proteoglycan Agrin is enriched within the early wound-microenvironment and is indispensable for efficient healing.