Knockdown of TRIM28 inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and migration

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Cellular Pathophysiology

Background:

• Atherosclerosis, a major cause of global mortality, involves changes in vascular smooth muscle cells.
• The role of Tripartite Motif-Containing 28 (TRIM28) in atherosclerosis pathogenesis is not well understood.
• Phenotypic switching of human aortic smooth muscle cells (HASMCs) is a critical event in atherosclerosis.

Purpose of the Study:

• To investigate the effect of TRIM28 on HASMC phenotypic switching.
• To elucidate the molecular mechanisms underlying TRIM28's role in PDGF-BB-induced HASMC changes.

Main Methods:

• TRIM28 expression analysis in human atherosclerotic tissues and cultured HASMCs.
• siRNA-mediated knockdown of TRIM28 in HASMCs.
• Assessment of HASMC proliferation, migration, and expression of VSMC markers (α-SMA, calponin, SM22α).
• Analysis of matrix metalloproteinase (MMP)-2 and MMP-9 expression.
• Evaluation of NF-κB signaling pathway activation.

Main Results:

• TRIM28 was highly expressed in atherosclerotic tissues and PDGF-BB-stimulated HASMCs.
• TRIM28 knockdown suppressed PDGF-BB-induced HASMC proliferation and migration.
• Knockdown of TRIM28 inhibited MMP-2 and MMP-9 expression.
• TRIM28 knockdown upregulated VSMC markers (α-SMA, calponin, SM22α).
• TRIM28 knockdown blocked PDGF-BB-induced NF-κB activation.

Conclusions:

• TRIM28 knockdown prevents PDGF-BB-induced phenotypic switching of HASMCs.
• TRIM28 inhibition may offer a therapeutic strategy for atherosclerosis.
• The findings suggest TRIM28 regulates HASMC phenotype via the NF-κB signaling pathway.