The dermal fibroblast is a crucial executor involved in wound healing, and lipopolysaccharide is a key factor in initiating the migration and proliferation of the dermal fibroblasts, followed by wound healing. However, the underlying molecular mechanism is still unknown. In this study, we demonstrated that stathmin increased concomitantly with p38/MAPK pathway activation by lipopolysaccharide stimulation of the human dermal fibroblast (HDF), which induced microtubule (MT) depolymerization followed by increased HDF migration and proliferation. In contrast, the application of taxol, the small interfering RNA transfection of stathmin, or the application of the p38/MAPK inhibitor SB203580 suppressed MT depolymerization and HDF migration and proliferation. Additionally, the overexpression of a MKK6(Glu) mutant, which constitutively activated p38/MAPK, resulted in MT depolymerization and, subsequently, promoted HDF migration and proliferation. Our data reveal a crucial role of stathmin in HDF migration and proliferation. These findings will provide new targets and strategies for clinical interventions in wound healing.

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Background Photodynamic therapy (PDT) is a promising new approach to promote wound healing and its effectiveness has been demonstrated in both clinical and animal studies. Macrophages are the key cells in wound healing and inflammatory response. However, the mechanism of action of PDT on macrophages in promoting wound healing is still unclear. Methods In this study, RAW264.7 cells were used. We analyzed the expression levels of macrophage markers arginase 1 (Arg‐1), CD206, iNOS, CD86, and inflammatory factors IL‐6, TNF‐α, and IL‐1β by reverse transcription‐polymerase chain reaction and Western blot, Milliplex microtubule‐associated protein multiplex assay was performed to analyze the expression of inflammatory factors in the supernatant. Live cell Imaging System to observe the dynamic process of macrophage phagocytosis. Western blot was performed to observe the activation of extracellular signal‐regulated kinase/mitogen‐activated protein kinase (ERK/MAPK) and NOD‐like receptor protein 3 (NLRP3) inflammasome. Results 5‐Aminolevulinic acid (ALA)‐PDT increased the expression of M1 marker iNOS/CD86 and decreased the expression of Arg‐1/CD206 in RAW264.7 cells, while, proinflammatory factors IL‐6, TNF‐α, and IL‐1β expression was enhanced and macrophage phagocytosis was increased. We also found that these phenomena were associated with activation of the ERK/MAPK‐NLRP3 pathway. Conclusion ALA‐PDT promotes early inflammatory responses by regulating macrophage M1 polarization through the ERK/MAPK‐NLRP3 pathway. It also promotes macrophage phagocytosis.