title: 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.
authors.affiliation: a Department of Anatomy , Yonsei University Wonju College of Medicine , Wonju , Republic of Korea.
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: a Department of Anatomy , Yonsei University Wonju College of Medicine , Wonju , Republic of Korea.
authors.forename: Yeo Wool
authors.initials: YW
authors.lastname: Kang
authors.affiliation: a Department of Anatomy , Yonsei University Wonju College of Medicine , Wonju , Republic of Korea.
authors.forename: Byung Young
authors.initials: BY
authors.lastname: Choi
authors.affiliation: a Department of Anatomy , Yonsei University Wonju College of Medicine , Wonju , Republic of Korea.
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Yang
authors.affiliation: a Department of Anatomy , Yonsei University Wonju College of Medicine , Wonju , Republic of Korea.
authors.forename: Byung Pil
authors.initials: BP
authors.lastname: Cho
authors.affiliation: a Department of Anatomy , Yonsei University Wonju College of Medicine , Wonju , Republic of Korea.
authors.forename: Won Gil
authors.initials: WG
authors.lastname: Cho
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D054413:Chemokine CCL11 / Q000235:genetics* / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D054397:Receptors, CCR3 / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D014945:Wound Healing / Q000235:genetics
chemical_list: C515458:Ccl11 protein, rat; C515352:Ccr3 protein, rat; D054413:Chemokine CCL11; D034741:RNA, Small Interfering; D054397:Receptors, CCR3; D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: CCL11; CCR3; HUVECs; angiogenesis; signaling pathway