The Role of the G Protein-Coupled Estrogen Receptor in Wound Healing

Estrogens regulate numerous physiological and pathological processes, including broad effects in wound healing. The effects of estrogens are mediated through estrogen receptors (ERs), which include the classical nuclear ERs (ERα and ERβ), which traditionally regulate gene expression, and the 7-transmembrane G protein-coupled estrogen receptor (GPER), which predominately mediates rapid “nongenomic” signaling. Estrogens can regulate epidermal function and regeneration, inflammation, and other functions that are vital to wound healing. We report that GPER is critical in wound healing, facilitating effects that are both dependent and independent of sex. GPER-deficiency is linked with an increase in skin necrosis, decrease in flap perfusion and changed vessel morphology. Together, these findings contribute to understanding GPER signaling in wound healing and suggest possible therapeutic opportunities by targeting GPER.