FAK Activation Promotes SMC Dedifferentiation via Increased DNA Methylation in Contractile Genes.

ABSTRACT:

Rationale

Vascular smooth muscle cells (SMCs) exhibit remarkable plasticity and can undergo dedifferentiation upon pathological stimuli associated with disease and interventions.

Objective

Although epigenetic changes are critical in SMC phenotype switching, a fundamental regulator that governs the epigenetic machineries regulating the fate of SMC phenotype has not been elucidated.

Methods and results

Using SMCs, mouse models, and human atherosclerosis specimens, we found that FAK (focal adhesion kinase) activation elicits SMC dedifferentiation by stabilizing DNMT3A (DNA methyltransferase 3A). FAK in SMCs is activated in the cytoplasm upon serum stimulation in vitro or vessel injury and active FAK prevents DNMT3A from nuclear FAK-mediated degradation. However, pharmaco

SUBMITTER: Jeong K 

PROVIDER: S-EPMC8639767 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature