CCL23 up-regulates expression of KDR/Flk-1 and potentiates VEGF-induced proliferation and migration of human endothelial cells.
CCL23 is a CC chemokine and exerts its biological activities on endothelial cells as well as on immune cells through CCR1. We investigated the potential effect of CCL23 on expression of KDR/Flk-1 receptor in endothelial cells. PCR, confocal microscope and Western blot analysis revealed that CCL23 up-regulated KDR/Flk-1 mRNA and protein levels in endothelial cells. A reporter assay indicated that CCL23-induced KDR/Flk-1 expression primarily occurred at the transcriptional level. In addition, CCL23 stimulated phosphorylation of SAPK/JNK, and an inhibitor of SAPK/JNK blocks the CCL23-induced KDR/Flk-1 expression. Furthermore, VEGF-induced ERK phosphorylation was stimulated by CCL23. Finally, CCL23 promoted VEGF-induced endothelial proliferation and migration, which were correlated with the maximal stimulation of KDR/Flk-1 expression by CCL23. Taken together, these findings suggest that CCL23 results in up-regulation of KDR/flk-1 receptor gene transcription and protein expression and that KDR/Flk-1 up-regulation induced by CCL23 may contribute to potentiation of VEGF action in angiogenesis.
Han
Kyu Yeon
KY
Graduate School of Biotechnology, College of Life Science, Kyung Hee University, 1 Seocheon-Ri Giheung-Eup, Yongin 446-701, Republic of Korea.
Kim
Chan Woo
CW
Lee
Tae Hoon
TH
Son
Youngsook
Y
Kim
Jiyoung
J
D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
C105504:CCL23 protein, human; D019742:Chemokines, CC; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4