Loureirin A Activates Wnt/beta-Catenin Pathway to Promote Wound with Follicle Stem Cell-Seeded Tissue-Engineered Skin Healing

摘要

Hair follicle stem cells (FSCs) can participate in the formation of hair follicles and epidermis. FSCs are well known as the ideal seed cells for tissue-engineered skin. Loureirin A, the major constituent of resina draconis, can promote skin wound healing. In this study, FSCs and hair follicle fibroblasts were combined with Pelnac (R) scaffold to construct tissue-engineered skin. The tissue-engineered skin was grafted into full-thickness skin defects of BALB/c-nu mice. Loureirin A was incorporated into the transplanted tissue-engineered skin. On day 3 of post-transplantation, loureirin A could inhibit inflammatory reaction. On day 7 of post-transplantation, loureirin A promoted the fibroblasts proliferation to repair dermis, and the newly formed epidermis was thicker than normal epidermis. On day 14 of post-transplantation, loureirin A promoted the newly formed skin tending to the normal skin. All of these results showed that loureirin A could promote skin wound repair. Wnt/beta-catenin pathway controls natural hair follicle regeneration and epidermis' repairing on skin injuries. In order to validate whether Wnt/beta-catenin pathway can be activated by loureirin A, it was used to stimulate FSCs in vitro. The results displayed that loureirin A could promote FSCs proliferation and change the cell cycle. Western blot showed that GSK-3 beta was down-regulated and beta-catenin was up-regulated in FSCs by loureirin A. Simultaneously, downstream genes of Wnt/beta-catenin pathway, c-Myc, cyclin D1, Tcf3 and Lef1, also increased. Overall, these results demonstrate that loureirin A activates Wnt/beta-catenin pathway and promotes FSC-seeded tissue-engineered skin to repair skin wound.