Quaking-cZFP609 Axis Remedies Aberrant Plasticity of Vascular Smooth Muscle Cells via Mediating Platelet-Derived Growth Factor Receptor β Degradation.

ABSTRACT: Vascular smooth muscle cell (VSMC) plasticity is crucial for the repair after vascular injury. However, the high plasticity of VSMCs may make them transform into pathogenic phenotypes. Here, we show that VSMCs overexpressing Sirtuin 1 (SIRT1) exhibit a reduced phenotypic plasticity in the context of platelet-derived growth factor (PDGF)-BB treatment. SIRT1 activated Quaking (QKI)-cZFP609 axis is involved in the plasticity regulation in the VSMCs. Mechanically, SIRT1 deacetylates K133 and K134 of QKI and mediates its activation. Activated QKI binds the QKI response elements located in the upstream and downstream of the cZFP609-forming exons in ZFP609 pre-mRNA to mediate cZFP609 production. Furthermore, the acetylation of QKI is increased by inhibiting SIRT1 with the selective and potent inh

SUBMITTER: Dou YQ 

PROVIDER: S-EPMC12000678 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature