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
de 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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Artériosclérose
/
Sphingosine
/
Lysophospholipides
/
Transduction du signal
/
Tunique intime
/
Sous-unités alpha G12-G13 des protéines G
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Protéine-61 riche en cystéine
/
Muscles lisses vasculaires
Type d'étude:
Prognostic_studies
/
Risk_factors_studies
Langue:
En
Journal:
Arterioscler Thromb Vasc Biol
Sujet du journal:
ANGIOLOGIA
Année:
2011
Type de document:
Article
Pays d'affiliation:
Corée du Sud