Tenascin‐c renders a proangiogenic phenotype in macrophage via annexin II

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.

Matrix-Targeting Immunotherapy Controls Tumor Growth and Spread by Switching Macrophage Phenotype

“…To determine whether macrophages responded differently to tenascin-C from different sources, we used an alternative experimental setup in which we grafted TNC + tumors into wild-type or tenascin-C knockout mice, where tumor cell-derived tenascin-C expression was kept constant. We observed a higher proportion of tumor-infiltrating macrophages in wildtype mice compared to knockout mice, consistent with the association of tenascin-C expression with macrophage infiltration in a range of other human [38] [39,40] [34], and its ability to promote macrophage migration in vitro [43].…”

Characterization of an Aggregated Three-Dimensional Cell Culture Model by Multimodal Mass Spectrometry Imaging

“…TNC is thought to promote survival and invasion by regulating the expression of proangiogenic factors such as vascular endothelial growth factor (VEGF) modulated by HIF-1α. 48 Additionally, TNC has been associated with inducing EMT changes with the downregulation of E-cadherin. 49 Thus, the TNC marker correlates with the distribution of the E-cadherin marker ( Figure 6 b).…”

Associations Between Tenascin-C and Testosterone Deficiency in Men with Major Depressive Disorder: A Cross-Sectional Retrospective Study

“… 37 TNC, for its part, affects the accumulation, apoptosis, and necrosis of macrophages. 38 In addition, testosterone may directly alter the expression and secretion of TNC, as shown in certain cancer cells. 39–42 Thus, reduced circulating testosterone levels may induce the expression of TNC in neurons or microglia of the central nervous system, which may contribute to MDD.…”