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Disruption of actin cytoskeleton mediates loss of tensile stress induced early phenotypic modulation of vascular smooth muscle cells in organ culture.
Zheng, Jian-Pu; Ju, Donghong; Shen, Jianbin; Yang, Maozhou; Li, Li.
Afiliação
  • Zheng JP; Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Exp Mol Pathol ; 88(1): 52-7, 2010 Feb.
Article em En | MEDLINE | ID: mdl-19874818
Aorta organ culture has been widely used as an ex vivo model for studying vessel pathophysiology. Recent studies show that the vascular smooth muscle cells (VSMCs) in organ culture undergo drastic dedifferentiation within the first few hours (termed early phenotypic modulation). Loss of tensile stress to which aorta is subject in vivo is the cause of this early phenotypic modulation. However, no underlying molecular mechanism has been discovered thus far. The purpose of the present study is to identify intracellular signals involved in the early phenotypic modulation of VSMC in organ culture. We find that the drastic VSMC dedifferentiation is accompanied by accelerated actin cytoskeleton dynamics and downregulation of SRF and myocardin. Among the variety of signal pathways examined, increasing actin polymerization by jasplakinolide is the only one hindering VSMC dedifferentiation in organ culture. Moreover, jasplakinolide reverses actin dynamics during organ culture. Latrunculin B (disrupting actin cytoskeleton) and jasplakinolide respectively suppressed and enhanced the expression of VSMC markers, SRF, myocardin, and CArG-box-mediated SMC promoters in PAC1, a VSMC line. These results identify actin cytoskeleton degradation as a major intracellular signal for loss of tensile stress-induced early phenotypic modulation of VSMC in organ culture. This study suggests that disrupting actin cytoskeleton integrity may contribute to the pathogenesis of vascular diseases.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Citoesqueleto / Actinas / Miócitos de Músculo Liso / Desdiferenciação Celular / Músculo Liso Vascular Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2010 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Citoesqueleto / Actinas / Miócitos de Músculo Liso / Desdiferenciação Celular / Músculo Liso Vascular Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2010 Tipo de documento: Article