PUBLICATION
Involvement of BIG1 and BIG2 in regulating VEGF expression and angiogenesis
- Authors
- Lu, F.I., Wang, Y.T., Wang, Y.S., Wu, C.Y., Li, C.C.
- ID
- ZDB-PUB-190615-11
- Date
- 2019
- Source
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology 33(9): 9959-9973 (Journal)
- Registered Authors
- Lu, Fu-I
- Keywords
- ARF1, ARFGEF, cell migration, endothelial cell, small GTPase
- MeSH Terms
-
- ADP-Ribosylation Factor 1/antagonists & inhibitors
- ADP-Ribosylation Factor 1/physiology
- Animals
- CRISPR-Cas Systems
- Cell Movement
- Embryo, Nonmammalian/blood supply
- Embryonic Development
- Endothelial Cells/cytology
- Endothelial Cells/metabolism
- Gene Knockdown Techniques
- Genes, Reporter
- Guanine Nucleotide Exchange Factors/antagonists & inhibitors
- Guanine Nucleotide Exchange Factors/genetics
- Guanine Nucleotide Exchange Factors/physiology*
- Human Umbilical Vein Endothelial Cells
- Humans
- Neovascularization, Physiologic/genetics
- Neovascularization, Physiologic/physiology*
- RNA Interference
- RNA, Small Interfering/genetics
- RNA, Small Interfering/pharmacology
- Vascular Endothelial Growth Factor A/biosynthesis*
- Vascular Endothelial Growth Factor A/genetics
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology
- PubMed
- 31199673 Full text @ FASEB J.
Citation
Lu, F.I., Wang, Y.T., Wang, Y.S., Wu, C.Y., Li, C.C. (2019) Involvement of BIG1 and BIG2 in regulating VEGF expression and angiogenesis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 33(9):9959-9973.
Abstract
VEGF stimulates the formation of new blood vessels by inducing endothelial cell (EC) proliferation and migration. Brefeldin A (BFA)-inhibited guanine nucleotide-exchange proteins (BIGs)1 and 2 accelerate the replacement of bound GDP with GTP to activate ADP-ribosylation factor (Arf)1, which regulates vesicular transport between the Golgi and plasma membrane. Although it has been reported that treating cells with BFA interferes with Arf1 activation to inhibit VEGF secretion, the role of BIG1 and BIG2 in VEGF trafficking and expression, EC migration and proliferation, and vascular development remains unknown. Here, we found that inactivation of Arf1 reduced VEGF secretion but did not affect the levels of VEGF protein. Interestingly, however, BIG1 and BIG2 knockdown significantly decreased the levels of VEGF mRNA and protein in glioblastoma U251 cells and HUVECs. Furthermore, depletion of BIG1 and BIG2 inhibited HUVEC angiogenesis by diminishing cell migration. Angioblast migration and intersegmental vessel sprouting were also impaired when the BIG2 homolog, Arf guanine nucleotide exchange factor (arfgef)2, was knocked down in zebrafish with endothelial expression of green fluorescent protein (GFP). Depletion of arfgef2 by clustered regularly interspaced short palindromic repeat/Cas9 also caused defects in vascular development of zebrafish embryos. Taken together, these data reveal that BIG1 and BIG2 participate in endothelial cell angiogenesis.-Lu, F.-I., Wang, Y.-T., Wang, Y.-S., Wu, C.-Y., Li, C.-C. Involvement of BIG1 and BIG2 in regulating VEGF expression and angiogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping