Functional interaction between CTGF and FPRL1 regulates VEGF-A-induced angiogenesis.

Autor: Lee MS; Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, South Korea., Ghim J; Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, South Korea., Kim SJ; Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, South Korea., Yun YS; Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, South Korea., Yoo SA; POSTECH-CATHOLIC BioMedical Engineering Institute, The Catholic University of Korea, Seoul 137-701, South Korea., Suh PG; Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, South Korea., Kim WU; Department of Internal Medicine, Division of Rheumatology, The Catholic University of Korea, Seoul 137-701, South Korea., Ryu SH; Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, South Korea. Electronic address: sungho@postech.ac.kr.
Jazyk: angličtina
Zdroj: Cellular signalling [Cell Signal] 2015 Jul; Vol. 27 (7), pp. 1439-48. Date of Electronic Publication: 2015 Apr 09.
DOI: 10.1016/j.cellsig.2015.04.001
Abstrakt: 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 Ca(2+) 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.
(Copyright © 2015 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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