MicroRNA-125b Affects Vascular Smooth Muscle Cell Function by Targeting Serum Response Factor

Area of Science:

• Molecular Biology
• Vascular Biology
• Biochemistry

Background:

• MicroRNAs (miRNAs) are increasingly implicated in the pathogenesis of peripheral vascular diseases.
• MicroRNA-125b (miR-125b) is significantly downregulated in human arteriosclerosis obliterans (ASO) arteries.
• The precise function of miR-125b in ASO development is not well understood.

Purpose of the Study:

• To investigate the expression, regulatory mechanisms, and functional role of miR-125b in arteriosclerosis obliterans (ASO).
• To explore the potential of targeting the miR-125b/SRF pathway for ASO treatment.

Main Methods:

• Vascular smooth muscle cells (VSMCs) were isolated and cultured.
• A rat carotid artery balloon injury model was established to mimic neointima formation.
• Lentiviral vectors were used to overexpress serum response factor (SRF) or miR-125b.
• Quantitative real-time PCR (qRT-PCR), Western blotting, in situ hybridization, CCK-8, EdU, transwell, wound closure, flow cytometry, and dual-luciferase reporter assays were employed.
• Immunohistochemistry and immunofluorescence were used to analyze protein expression and localization.

Main Results:

• miR-125b expression was reduced in ASO arteries and PDGF-BB-stimulated VSMCs.
• Overexpression of miR-125b inhibited VSMC proliferation and migration while promoting apoptosis.
• Serum response factor (SRF) was identified as a direct target of miR-125b.
• Exogenous miR-125b modulated SRF expression and reduced neointimal formation in a rat model.

Conclusions:

• The miR-125b/SRF pathway plays a critical role in regulating VSMC function during ASO.
• Modulating miR-125b levels presents a promising novel therapeutic strategy for treating arteriosclerosis obliterans.