Expression of CXCL1 in human endothelial cells induces angiogenesis through the CXCR2 receptor and the ERK1/2 and EGF pathways

Abstract

Endothelial cell growth and proliferation are critical for angiogenesis; thus, greater insight into the regulation of pathological angiogenesis is greatly needed. Previous studies have reported on chemokine (C-X-C motif) ligand 1 (CXCL1) expression in epithelial cells and that secretion of CXCL1 from these epithelial cells induces angiogenesis. However, limited reports have demonstrated CXCL1 expression in endothelial cells. In this report, we present data that expand on the role of CXCL1 in human endothelial cells inducing angiogenesis. Specifically, CXCL1 is expressed and secreted from human endothelial cells. Interference of CXCL1 function using neutralizing antibodies resulted in a reduction in endothelial cell migration and viability/proliferation, the latter associated with a decrease in levels of cyclin D and cdk4. In vitro studies revealed that CXCL1 influenced neoangiogenesis through the regulation of epidermal growth factor and ERK1/2. In a xenograft angiogenesis model, interference of CXCL1 function resulted in inhibition of angiogenesis. A better understanding of the role of CXCL1 in the interactions between the endothelial and epithelial components will provide insight into how human tissues use CXCL1 to survive and thrive in a hostile environment.

Active Ingredients of Hange-shashin-to, Baicalelin and 6-Gingerol, Inhibit 5-Fluorouracil-Induced Upregulation of CXCL1 in the Colon to Attenuate Diarrhea Development

“…[19][20][21] Although we showed that the CXCL1 expression in distal colon was enhanced by 5-FU, the cell which CXCL1 upregulated by 5-FU was not identified in the current study. Therefore, a further study is necessary.…”

CXCL1 promotes tumor growth through VEGF pathway activation and is associated with inferior survival in gastric cancer

“…Miyake et al [32] reported that secretion of CXCL1 from epithelial cells induced angiogenesis. CXCL1 increased VEGF expression and cell migration in vitro which was blocked by VEGF-siRNA and VEGF neutralizing antibody.…”

IL-17A, But Not IL-17F, Is Indispensable for Airway Vascular Remodeling Induced by Exaggerated Th17 Cell Responses in Prolonged Ovalbumin-Challenged Mice

“…Thus, we hypothesize that, in addition to the direct chemotactic effect of IL-17A, EPC recruitment induced by IL-17A in vivo is also related to the activation of CXCR2. In addition, Miyake et al (30) reported that CXCL1 was related to the viability of endothelial cells and induced migration and tube formation via the ERK1/2 signaling pathway. Thus, we propose that CXCL1 is also involved in angiogenesis of endothelial cells.…”