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Mol Cells ; 43(8): 749-762, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32868491

RESUMO

The migration, dedifferentiation, and proliferation of vascular smooth muscle cells (VSMCs) are responsible for intimal hyperplasia, but the mechanism of this process has not been elucidated. WD repeat domain 1 (WDR1) promotes actin-depolymerizing factor (ADF)/cofilin-mediated depolymerization of actin filaments (F-actin). The role of WDR1 in neointima formation and progression is still unknown. A model of intimal thickening was constructed by ligating the left common carotid artery in Wdr1 deletion mice, and H&E staining showed that Wdr1 deficiency significantly inhibits neointima formation. We also report that STAT3 promotes the proliferation and migration of VSMCs by directly promoting WDR1 transcription. Mechanistically, we clarified that WDR1 promotes the proliferation and migration of VSMCs and neointima formation is regulated by the activation of the JAK2/STAT3/WDR1 axis.


Assuntos
Proteínas dos Microfilamentos/deficiência , Animais , Artérias Carótidas/citologia , Artérias Carótidas/metabolismo , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Janus Quinase 2/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/metabolismo , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Neointima/metabolismo , Neointima/patologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Repetições WD40
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