A variety of mediators such as cytokines and chemokines properly regulate the process of skin wound repair. Previous study indicated that cytoplasmic DNA-sensor cyclic GMP-AMP synthase (cGAS) activates the stimulator of interferon genes (STING) through production of cyclic GMP-AMP (cGAMP) and is followed by inducing inflammatory cytokines, including type I interferon (IFN). In the present study, we evaluated whether activation of the STING pathway by cGAMP affects the process of skin wound repair. We established the skin wound repair model using wild-type (WT) mice. Two full-thickness excisional punch biopsies were taken from the right and left subscapular regions. One site was treated with ointment containing cGAMP, and the other was treated with a control ointment. Changes in wound closure over time were calculated using photography. Topical administration with cGAMP markedly accelerated skin wound healing up to day 6. Moreover, treatment with cGAMP on wound sites activated STING signaling pathway and increased the expression of IFN-β, CXCL10 and CCL2 in the wound sites compared to treatment with control ointment. The scratch assay also showed that cGAMP treatment accelerated wound closure in mouse embryonic fibroblasts. The administration of anti-IFNR antibody or anti-CXCR3 antibody impaired the acceleration of skin wound repair by cGAMP. These results demonstrated that topical treatment with cGAMP accelerates skin wound healing by inducing type I IFN and activating the CXCL10/CXCR3 pathway. Topical administration of cGAMP might make a contribution to new effective treatments for accelerating skin wound healing.

Activation of STING signaling accelerates skin wound healing by activation of the CXCL10/CXCR3 pathway