G(alpha)12/13 induction of CYR61 in association with arteriosclerotic intimal hyperplasia: effect of sphingosine-1-phosphate.
Arterioscler Thromb Vasc Biol
; 31(4): 861-9, 2011 Apr.
Article
en En
| MEDLINE
| ID: mdl-21212405
ABSTRACT
OBJECTIVE:
Gα(12/13) play a role in oncogenic transformation and tumor growth. Cysteine-rich protein 61 (CYR61) is a growth-factor-inducible angiogenic factor. In view of potential overlapping functions between Gα(12/13) and CYR61, this study investigated the role of these G proteins in CYR61 induction in association with hyperplastic vascular abnormality. METHODS ANDRESULTS:
Overexpression of activated Gα(12) or Gα(13) induced CYR61 expression in vascular smooth muscle cells (VSMCs). Gene knockdown and knockout experiments revealed that sphingosine-1-phosphate (S1P) treatment induced CYR61 via Gα(12/13). JunD/activator protein-1 (AP-1) was identified as a transcription factor required for CYR61 transactivation by S1P. Deficiencies in Gα(12/13) abrogated AP-1 activation and AP-1-mediated CYR61 induction. c-Jun N-terminal kinase was responsible for CYR61 induction. Moreover, deficiencies of Gα(12/13) abolished c-Jun N-terminal kinase-dependent CYR61 induction by S1P. N-acetyl-l-cysteine or NADPH oxidase inhibitor treatment reversed CYR61 induction by S1P, indicating that reactive oxygen species are responsible for this process. The levels of Gα(12/13) were increased within thickened intimas and medias in wire-injured mouse femoral arteries, which was accompanied by simultaneous CYR61 induction. Moreover, Gα(12/13) and CYR61 were costained in the arteriosclerotic lesions immediately adjacent to human tumor tissues.CONCLUSIONS:
Gα(12/13) regulate AP-1-dependent CYR61 induction in VSMCs and promote VSMC migration, and they are upregulated with CYR61 in arteriosclerotic lesions.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Arteriosclerosis
/
Esfingosina
/
Lisofosfolípidos
/
Transducción de Señal
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Túnica Íntima
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Subunidades alfa de la Proteína de Unión al GTP G12-G13
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Proteína 61 Rica en Cisteína
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Músculo Liso Vascular
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Asunto de la revista:
ANGIOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Corea del Sur