MMP9 secreted from mononuclear cell quality and quantity culture mediates STAT3 phosphorylation and fibroblast migration in wounds

单核细胞质量和数量培养分泌的 MMP9 介导伤口中的 STAT3 磷酸化和成纤维细胞迁移

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作者:Tsubame Nishikai-Yan Shen, Makiko Kado, Hiroko Hagiwara, Satoshi Fujimura, Hiroshi Mizuno, Rica Tanaka

Conclusions

MNC-QQc cells promote wound healing by the secretion of MMP9, which induces fibroblast migration via the STAT3 signaling pathway.

Methods

After separation from a 50 mL blood sample from healthy individuals, mononuclear cells were cultured for 7 days in a serum-free ex vivo expansion system with five different cytokines (MNC-QQc method). The effects of MNC-QQc cells on human dermal fibroblast migration were observed by scratch assay. An angiogenesis array screened the MNC-QQc cell supernatant for proteins related to wound healing. Finally, fibroblast migration was confirmed by observing the intracellular signal transduction pathways via Western blot.

Results

The migration of fibroblasts co-cultured with MNC-QQc cells increased by matrix metallopeptidase-9 (MMP9) secretion, as suggested by the angiogenesis array. Furthermore, the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in fibroblast/MNC-QQc cell co-culture and fibroblast culture with added recombinant human MMP9 protein increased. When fibroblasts were cultured with either an MMP9 inhibitor or a STAT3 inhibitor, both fibroblast migration and STAT3 phosphorylation were significantly suppressed. Conclusions: MNC-QQc cells promote wound healing by the secretion of MMP9, which induces fibroblast migration via the STAT3 signaling pathway.

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