IGFBP-7 secreted by adipose-derived stem cells inhibits keloid formation via the BRAF/MEK/ERK signaling pathway

Adipose tissue-derived stem cells (ASCs) have important clinical significance as regulators of skin scar tissue regeneration. ASCs inhibit keloid formation and increase insulin-like growth factor-binding protein-7 (IGFBP-7) expression. However, whether ASCs inhibit keloid formation through IGFBP-7 remains unclear.We aimed to assess the roles of IGFBP-7 in keloid formation.We analyzed the proliferation, migration, and apoptosis of keloid fibroblasts (KFs) treated with recombinant IGFBP-7 (rIGFBP-7) or by co-culture with ASCs using CCK8 assays, transwell assays, and flow cytometry, respectively. In addition, immunohistochemical staining, quantitative polymerase chain reaction, human umbilical vein endothelial cell tube formation, and western blotting experiments were used to assess keloid formation.IGFBP-7 expression was significantly lower in keloid tissues than that in normal skin tissues. Stimulation of KFs with rIGFBP-7 at different concentrations or by co-culture with ASCs resulted in decreased KF proliferation. Additionally, KF stimulation with rIGFBP-7 resulted in increased apoptosis of KFs. IGFBP-7 also reduced angiogenesis in a concentration-dependent manner, and stimulation with different rIGFBP-7 concentrations or co-culture of KFs with ASCs inhibited the expression of transforming growth factor-β1, vascular endothelial growth factor, collagen I, interleukin (IL)-6, IL-8, B-raf proto-oncogene (BRAF), mitogen-activated protein kinase kinase (MEK), and extracellular signal-regulated kinase (ERK) in KFs.Collectively, our findings suggested that ASC-derived IGFBP-7 prevented keloid formation by inhibiting the BRAF/MEK/ERK signaling pathway.