Low-power laser irradiation (LPLI) promotes VEGF expression and vascular endothelial cell proliferation through the activation of ERK/Sp1 pathway.
Angiogenesis, the growth of new blood vessels from pre-existing vessels, represents an excellent therapeutic target for the treatment of wound healing and cardiovascular disease. Herein, we report that LPLI (low-power laser irradiation) activates ERK/Sp1 (extracellular signal-regulated kinase/specificity protein 1) pathway to promote VEGF expression and vascular endothelial cell proliferation. We demonstrate for the first time that LPLI enhances DNA-binding and transactivation activity of Sp1 on VEGF promoter in vascular endothelial cells. Moreover, Sp1-regulated transcription is in an ERK-dependent manner. Activated ERK by LPLI translocates from cytoplasm to nuclear and leads to increasing interaction with Sp1, triggering a progressive phosphorylation of Sp1 on Thr453 and Thr739, resulting in the upregulation of VEGF expression. Furthermore, selective inhibition of Sp1 by mithramycin-A or shRNA suppresses the promotion effect of LPLI on cell cycle progression and proliferation, which is also significantly abolished by inhibition of ERK activity. These findings highlight the important roles of ERK/Sp1 pathway in angiogenesis, supplying potential strategy for angiogenesis-related diseases with LPLI treatment.
MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China.
Jie
J
Feng
Yingjie
Y
Zhang
Da
D
Xing
D049109:Cell Proliferation; D004247:DNA / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D004789:Enzyme Activation; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D028022:Low-Level Light Therapy; D020935:MAP Kinase Signaling System; D018919:Neovascularization, Physiologic; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D016329:Sp1 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; D004247:DNA