Shear stress-activated MMP-2 promotes BMSCs migration via the LIMK1/Cofilin axis during vascular remodeling.

Shear stress enhances matrix metalloproteinase-2 (MMP-2) expression, which plays a critical role in bone marrow mesenchymal stem cells (BMSCs) migration and vascular remodeling via microenvironmental interactions with mouse aortic endothelial cells (MAECs). MAECs were exposed to disturbed flow using a custom flow device for 1, 3, or 5 h, and conditioned media (MAEC-CM) were collected. BMSCs migration in response to different MAEC-CM conditions was assessed by flow cytometry, transwell, and wound-healing assays. MMP-2 levels in MAEC-CM were modulated with recombinant protein or neutralizing antibody. LIMK1/Cofilin pathway activation was evaluated by western blot, and the LIMK1 inhibitor BMS-3 was used to confirm pathway function. Disturbed flow altered MAECs density, morphology, and intercellular gaps, with apoptosis increasing over time. ELISA showed MMP-2 secretion peaked at 3 h, coinciding with maximal BMSCs migration. Recombinant MMP-2 (400 ng/mL) further enhanced, while MMP-2 neutralizing antibody (100 ng/mL) suppressed, migration induced by MAEC-CM-3 h. Western blot revealed significant phosphorylation of LIMK1 and Cofilin after MAEC-CM-3 h treatment, with higher levels in recombinant MMP-2-treated groups compared to neutralization. BMS-3 significantly reduced MMP-2-induced BMSCs migration and phosphorylation of LIMK1/Cofilin without affecting total protein levels. These results indicate that shear stress-induced MMP-2 promotes BMSCs motility through LIMK1-dependent Cofilin activation. This study not only clarifies the molecular mechanism by which disturbed flow regulates BMSCs migration but also provides a theoretical basis for BMSC-mediated vascular repair, offering potential targets for future clinical applications.

• Publication year

  2025

• Venue

  Microvascular Research

• Publication date

  2025-08-01

• Fields of study

  Medicine, Environmental Science

• Identifiers
  DOI 10.1016/j.mvr.2025.104863PMID 40882768
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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