GRK2 deletion improves the function of skin flap following ischemia-reperfusion injury by regulating Drp1.

Skin flap ischemia-reperfusion (IR) injury is the key factor to the success rate of skin transplantation, the molecular mechanism of flap IR injury needs to be continuously explored to provide new ideas for its clinical treatment. G protein-coupled receptor kinase 2 (GRK2) was reported to be involved in regulating mitochondrial function, and mitochondria were essential in the process of flap IR. Thus, we aimed to investigate the function of GRK2 in flap ischemia-reperfusion injury and further explore the underlying mechanism. Sixty male C57BL/6 mice were randomly divided into four groups: sham, IR+sh-NC, IR+sh-GRK2 and IR+sh-GRK2+ dynamin-related GTPase 1 (Drp1). Flap function and mitochondrial function were determined after ischemia for 3 hours and reperfusion for 72 hours. Comparing with sham group, GRK2 was increased in flap after IR injury. Loss of GRK2 inhibited cell apoptosis and promoted cell proliferation of flap after IR injury. And deficiency of GRK2 promoted mitochondrial function in flap after IR injury. IR injury up-regulated Drp1 expression in flap, while sh-GRK2 down-regulated Drp1 expression. Furthermore, overexpression of Drp1 removed the protective effect of sh-GRK2. In conclusion, our study revealed that GRK2 deletion improved flap function and mitochondrial function by inhibiting Drp1 expression, which may provide a new insight for the clinical treatment of flap ischemia-reperfusion injury.