Background
Skin wound healing is a challenging problem, especially in aging or diabetic patients, which becomes more difficult to heal, and easily
Conclusion
Metformin regulated AMPK/mTOR singling pathway to inhibit NLRP3 inflammasome activation, which boosted M2 macrophage polarization to accelerate the wound healing. These findings provided new insights into the molecular mechanism of metformin therapy and its therapeutic potential in wound healing.
Methods
Metformin was local topical application in rat skin defect models. Alterations in the wounded skin were observed, and angiogenesis in the wound also was analyzed by immunohistochemical staining. The markers associated with differentiation macrophage were analyzed by immunofluorescence staining. The roles of AMPK singling pathway and the relative protein of NLRP3 inflammasome in wound were also analyzed by western blotting. In addition, AMPK/mTOR/NLRP3 inflammasome signaling axis was investigated to further analyze the molecular mechanism of metformin treatment on inducing M2 macrophage polarization in vitro.
Results
Out results showed that metformin improved wound healing and angiogenesis which was paralleled by M2 macrophage polarization. We also found that the level of relative proteins of NLRP3 inflammasome was markedly decreased after metformin treatment. Furthermore, blockage of AMPK or activation of mTOR abolished the effects of metformin treatment on depressing NLRP3 inflammasome activation, M2 polarization and improving wound healing. It suggested that the treatment effects of metformin on wound healing were through regulating AMPK/mTOR/NLRP3 inflammasome signaling axis.