Rho/MRTF-A-Induced Integrin Expression Regulates Angiogenesis in Differentiated Multipotent Mesenchymal Stem Cells

Area of Science:

• Cell Biology
• Molecular Biology
• Regenerative Medicine

Background:

• Mesenchymal stem cells (MSCs) differentiate into endothelial cells with vascular endothelial growth factor (VEGF) treatment.
• The angiogenic potential of MSCs and the underlying molecular mechanisms require further elucidation.
• Integrins alpha1beta1 and alpha5beta1 are key mediators in both physiological and pathological angiogenesis.

Purpose of the Study:

• To investigate the role of the Rho/MRTF-A signaling pathway in MSC-mediated angiogenesis.
• To determine the effect of Rho/MRTF-A signaling on the expression of integrins alpha1beta1 and alpha5beta1.
• To elucidate the regulatory mechanism of MRTF-A on integrin gene promoters.

Main Methods:

• MSCs were induced to undergo endothelial differentiation.
• Expression levels of integrins alpha1, alpha5, and beta1 were analyzed.
• Rho/MRTF-A signaling pathway activity was modulated using inhibitors (C3 transferase, Y27632) and shRNA (shMRTF-A).
• Luciferase reporter and ChIP assays were employed to assess MRTF-A binding to integrin promoters.
• Cell migration and in vitro vessel network formation assays were performed in human umbilical vein endothelial cells (HUVECs).

Main Results:

• Increased expression of integrins alpha1, alpha5, and beta1 was observed during MSC angiogenesis.
• The Rho/MRTF-A pathway was confirmed to regulate the expression of these integrins.
• MRTF-A directly binds to and transactivates the integrin alpha1 and alpha5 promoters.
• Inhibition of Rho/MRTF-A signaling suppressed integrin upregulation and angiogenesis.
• MRTF-A deletion in HUVECs significantly reduced cell migration and vessel formation.

Conclusions:

• The Rho/MRTF-A signaling pathway plays a critical role in MSC-mediated angiogenesis.
• This pathway regulates angiogenesis by controlling the expression of integrins alpha1beta1 and alpha5beta1.
• Targeting the Rho/MRTF-A pathway offers a potential strategy for modulating MSC angiogenic activity.