Fig 2: SF MNs alter the mechanical communication between fibroblasts and the surrounding matrix and result in a cascade of cellular responses. (A) Illustration of SF MN interrupting the mechanical communication between fibroblasts and the ECM to prevent fibroblast activation and promoting ECM remodeling with reduced secretions of collagen I and fibronectin via the integrin–FAK signaling pathway. (B) Western blotting of integrin, FAK, RhoA, and F-actin assembly, as well as type I collagen and fibronectin involved in the ECM network in fibroblasts with the treatment of FAKI, SF MNs, and FAKI + SF MNs. (C) Semiquantitative statistics of protein levels from Western blotting of (B). ##p < 0.001, n = 3. (D) CLSM of the intracellular F-actin meshwork of fibroblasts under different treatments. Blue signals: nucleus; green signals: F-actin. Scale bar, 100 μm.

Fig 3: 152RM induces the migration of MSCs partly through the FAK/STAT3 signaling pathway. (A) Transwell assays for the migration of MSCs using 152RM (n = 5 each). Representative crystal violet staining images are shown in the left panel. Quantification of cell migration is shown in the right panel. Scale bar, 100 μm. (B) RNA-seq analysis showed the alteration of cell migration-specific gene expression in MSCs cultured with 152RM (n = 3 each). (C) Relative mRNA expression levels of cell migration-specific genes in MSCs cultured with 152RM (n = 5 each). (D) Quantification of the transwell assay and cell wound scratch assay after culture with 152RM, a CXCR4 inhibitor (AMD3100) and an Integrin αvβ3 inhibitor (Cyclo(-RGDfK)) (n = 5 each). (E) Western blot analysis of the expression of E-cadherin in MSCs after the addition of 152RM (n = 5 per group). (F) Gene set enrichment analysis (GSEA) plots showing upregulation of the JAK/STAT signaling pathway in MSCs cultured with 152RM (n = 3 each). (G) RNA-seq analysis showed alterations in JAK/STAT signaling pathway-related gene expression in MSCs cultured with 152RM (n = 3 each). (H) Western blot analysis of the expression of CXCR4, integrin αvβ3, p-Jak2, Jak2, p-FAK, FAK, p-STAT3 and STAT3 in MSCs (pretreated with a CXCR4 inhibitor (AMD3100) and an integrin αvβ3 inhibitor (cyclo(-RGDfK))) after the addition of 152RM (n = 5 per group). Data are shown as the mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.001; ANOVA and Student's t-test were employed. For all panels in this figure, data are representative of three independent experiments.

Fig 4: 152RM induces ECs migration partly through the FAK/ERK signaling pathway. (A) Transwell assay for the migration of ECs using 152RM (n = 5 each). Scale bar, 100 μm. Quantification of cell migration was performed (right). (B) Relative mRNA expression levels of cell migration-specific genes in ECs cultured with 152RM (n = 5 each). (C) Representative immunostaining images of p-VEGFR2 (red) ECs with or without 152RM (n = 5 per group). Scale bar, 100 μm. (D) Quantification of transwell assays after culture with 152RM, a VEGFR2 inhibitor (Ki8751) and an integrin αvβ3 inhibitor cyclo(-RGDfK) (n = 5 each). (E) Western blot analysis of the expression of integrin αvβ3, p-VEGFR2, p-FAK, FAK, p-ERK1/2 and ERK1/2 in ECs (pretreated with a VEGFR2 inhibitor (Ki8751) and an integrin αvβ3 inhibitor (cyclo(-RGDfK))) after the addition of 152RM (n = 5 per group). (F) Schematic illustration of the role of 152RM in promoting ECs migration. Data are shown as the mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.001; ANOVA and Student's t-test were employed. For all panels in this figure, data are representative of three independent experiments.

Fig 5: Mechanism of GU injury and repair by EA. Injury: Gastric ulcer pathogenesis involves acid and pepsin hypersecretion, disrupting the mucosal integrity and triggering inflammatory and apoptotic cascades that propagate tissue damage. Repair: The repair involves four phases: localized flaws, extensive atrophy and dissociation of gastric epithelial cells, cell adhesion and tissue colonization, and cell aggregation with tissue remodeling, with pivotal adhesive junction reconstruction. EA enhances cell-matrix adhesion via EGFR/FAK-Src signaling, promoting focal adhesion protein (integrin/paxillin/talin) assembly to reorganize cytoskeletal networks and the extracellular matrix, ultimately restoring mucosal barrier integrity.