Functional interaction between CTGF and FPRL1 regulates VEGF-A-induced angiogenesis
SCIE
SCOPUS
- Title
- Functional interaction between CTGF and FPRL1 regulates VEGF-A-induced angiogenesis
- Authors
- Lee, MS; Ghim, J; Kim, SJ; Yun, YS; Yoo, SA; Suh, PG; Kim, WU; Ryu, SH
- Date Issued
- 2015-07
- Publisher
- ELSEVIER SCIENCE INC
- Abstract
- Vascular endothelial growth factor-A (VEGF-A) is a master regulator of angiogenesis that controls several angiogenic processes in endothelial cells. However, the detailed mechanisms of VEGF-A responsible for pleiotropic functions and crosstalk with other signaling pathways have not been fully understood. Here, we found that VEGF-A utilizes the connective tissue growth factor (CTGF)/formyl peptide receptor-like 1 (FPRL1) axis as one of its mediators in angiogenesis. Using a proteomic approach, we found increased secretion of a matricellular protein, CTGF, from VEGF-A-treated human umbilical vein endothelial cells (HUVECs). Then, we studied the effect of CTGF binding to FPRL1 in VEGF-A-induced angiogenesis. CTGF directly binds to FPRL1 through a linker region and activates the downstream signals of FPRL1, such as increase in extracellular signal-regulated kinase (ERK) phosphorylation and intracellular Ca2+ concentration. We found that linker region-induced FPRL1 activation promotes the migration and network formation of HUVECs, while disruption of FPRL1 inhibits VEGF-A-induced HUVEC migration and network formation. In addition, similar results were observed by the chorioallantoic membrane (CAM) assay based evaluation of angiogenesis in vivo. To summarize, our data reveal a novel working model for VEGF-A-induced angiogenesis via the VEGF-A/CTGF/FPRL1 axis that might prolong and enhance the signals initiated from VEGF-A. (C) 2015 Elsevier Inc All rights reserved.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/35471
- DOI
- 10.1016/J.CELLSIG.2015.04.001
- ISSN
- 0898-6568
- Article Type
- Article
- Citation
- CELLULAR SIGNALLING, vol. 27, no. 7, page. 1439 - 1448, 2015-07
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