Fig. 3

Signaling pathways of MSCs-driven intracellular ECM. Signaling pathways of MSCs-driven intracellular ECM. In the TGF-β/SMAD pathway, BMSCs-EVs load miR-328a-3p into fibroblasts. miR-328a-3p downregulates SIRT7 expression, which in turn promotes the binding of phosphorylated SMAD2/3 to SMAD4 into the nucleus and promotes the expression of elastin, collagen I, and III. In the JAK/STAT pathway, cytokines and GFs secreted by BMSCs bind to target cell receptors and activate JAK2-STAT4 phosphorylation, and p-STAT4 forms a dimer to enter the nucleus and promote collagen I and III expression. In the Wnt/β-catenin pathway, miR-3960 loaded by MSCs-EVs entered the target cells and down-regulated PHLDA2, inhibiting ECM degradation induced by this substance. In the PI3K/AKT pathway, IGF-1 secreted by MSCs activated PI3K-AKT-mTOR phosphorylation and regulated intracytoplasmic protein synthesis. In the ERK/MAPK pathway, VEGF secreted by MSCs can activate Ras-Raf-MEK-ERK1/2 phosphorylation, which promotes the expression of collagen I and III in the nucleus and regulates protein synthesis in the cytoplasm