CCL11 promotes angiogenic activity by activating the PI3K/Akt pathway in HUVECs

Abstract

CCR3, the receptor for CCL11, is expressed on the surface of immune cells and even on non-immune cells. CCL11-CCR3 interactions can promote cell migration and proliferation. In this study, we investigated the effect of CCL11 on angiogenesis in HUVECs and also examined the molecular mechanisms of this process. We found that CCL11 induced mRNA transcription and protein expression of CCR3 in HUVECs. Moreover, the scratch wound healing assay and MTS proliferation assay both demonstrated that CCL11 promotes endothelial cell migration and induces weak proliferation. CCL11 directly induced microvessel sprouting from the rat aortic ring; these effects occurred earlier and to a greater extent than with VEGF stimulation. Furthermore, CCL11-induced phosphorylation of Akt was abolished by PI3K inhibitors. siRNA-mediated knockdown of CCR3 led to a significant reduction of PI3K phosphorylation. However, the phosphorylation levels of ERK1/2 were not changed, even after CCL11 treatment. Cumulatively, our data suggest that the CCL11–CCR3 interaction mainly activates PI3K/Akt signal transduction pathway in HUVECs.

Keywords:

• CCR3
• CCL11
• signaling pathway
• angiogenesis
• HUVECs

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This study was supported by a grant from the National Research Foundation of Korea, which is funded by the Korean Government [NRF-2011-0013109], Yonsei University research grant [Grant no. 2012-62-5060] and Yonsei University Wonju College of Medicine [YUWCM-2010-15].