Open AccessTenascin‐c renders a proangiogenic phenotype in macrophage via annexin II
Author(s) -
Wang Zhiyang,
Wei Qi,
Han Liang,
Cao Keqing,
Lan Tianfeng,
Xu Zhenjie,
Wang Yingjuan,
Gao Yuan,
Xue Jing,
Shan Fei,
Feng Jun,
Xie Xin
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13332
Subject(s) - tenascin , annexin a2 , annexin a5 , macrophage , annexin , tenascin c , extracellular matrix , macrophage polarization , annexin a1 , chemistry , microbiology and biotechnology , western blot , cancer research , biology , fibronectin , flow cytometry , biochemistry , in vitro , gene
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% O 2 ) for 12 hrs or hypoxic condition (1% O 2 ) 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.