Neutrophil extracellular traps with low concentrations induce proliferation and migration of human fibroblasts via activating CCDC25/ILK/PI3K/AKT pathway

Neutrophil plays an important role in the early stage of wound healing. Excessive neutrophil extracellular traps (NETs) which are produced by neutrophil have been proved as a significant unfavorable factor for wound healing by impairing the function of human skin fibroblasts. However, the effect of NETs with low concentrations on fibroblasts remains unclear. The interaction between CCDC25 and ILK in fibroblast were found to be activated by NET-DNA with low concentrations. Additionally, phosphorylation of PI3K and AKT was increased in NET-stimulated fibroblasts but was inhibited by CCDC25 knockout or ILK knockdown. NETs-induces proliferation and migration ability of fibroblast were also reduced by application of CCDC25 sgRNAs or ILK shRNAs. This study demonstrates that low concentrations of NETs, upon biding with CCDC25, activates the ILK/PI3K/AKT signaling pathway in skin fibroblasts, leading to increased cell proliferation and migration activity.