EDA Fibronectin Microarchitecture and YAP Translocation During Wound Closure
September 2024
Studysummary This study found that culturing fibroblasts on stiffer substrates mimicking fibrotic wounds led to an aligned EDA fibronectin matrix with thinner fibers and decreased YAP activity, suggesting disrupted signaling that might be restored to promote regenerative wound repair.
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This study investigates the role of EDA fibronectin (Fn) organization in modulating YAP translocation during wound closure, focusing on differences between normal and fibrotic conditions. Human dermal fibroblasts were cultured on substrates mimicking normal (18 kPa) and fibrotic (146 kPa) skin. On stiffer substrates, fibroblasts formed aligned EDA Fn matrices with thinner fibers, indicating increased tension. Inhibiting EDA domain binding with Irigenin or suppressing YAP activity with CA3 led to randomly organized matrices with thicker fibers, suggesting reduced tension. YAP activity increased on softer substrates but decreased on stiffer ones, with treatments restoring YAP activity on stiffer substrates. The findings suggest disrupted signaling between EDA Fn organization and YAP translocation in fibrotic wound closure, which could be corrected to promote regenerative repair.
