Tenascin-c renders a proangiogenic phenotype in macrophage via annexin II.
J Cell Mol Med
; 22(1): 429-438, 2018 01.
Article
em En
| MEDLINE
| ID: mdl-28857429
ABSTRACT
Tenascin-c is an extracellular matrix glycoprotein, the expression of which relates to the progression of atherosclerosis, myocardial infarction and heart failure. Annexin II acts as a cell surface receptor of tenascin-c. This study aimed to delineate the role of tenascin-c and annexin II in macrophages presented in atherosclerotic plaque. Animal models with atherosclerotic lesions were established using ApoE-KO mice fed with high-cholesterol diet. The expression of tenascin-c and annexin II in atherosclerotic lesions was determined by qRT-PCR, Western blot and immunohistochemistry analysis. Raw 264.7 macrophages and human primary macrophages were exposed to 5, 10 and 15 µg/ml tenascin-c for 12 hrs. Cell migration as well as the proangiogenic ability of macrophages was examined. Additionally, annexin II expression was delineated in raw 264.7 macrophages under normal condition (20% O2 ) for 12 hrs or hypoxic condition (1% O2 ) for 6-12 hrs. The expression of tenascin-c and annexin II was markedly augmented in lesion aorta. Tenascin-c positively regulated macrophage migration, which was dependent on the expression of annexin II in macrophages. VEGF release from macrophages and endothelial tube induction by macrophage were boosted by tenascin-c and attenuated by annexin II blocking. Furthermore, tenascin-c activated Akt/NF-κB and ERK signalling through annexin II. Lastly, hypoxia conditioning remarkably facilitates annexin II expression in macrophages through hypoxia-inducible factor (HIF)-1α but not HIF-2α. In conclusion, tenascin-c promoted macrophage migration and VEGF expression through annexin II, the expression of which was modulated by HIF-1α.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anexina A2
/
Tenascina
/
Neovascularização Fisiológica
/
Macrófagos
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Animals
/
Humans
/
Middle aged
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article