Involvement of BIG1 and BIG2 in regulating VEGF expression and angiogenesis
| Autor: | Chang Yi Wu, Fu I. Lu, Chun Chun Li, Yi Ting Wang, Yi Shan Wang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Vascular Endothelial Growth Factor A
0301 basic medicine Embryo Nonmammalian Angiogenesis Embryonic Development Neovascularization Physiologic Angioblast Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Movement Genes Reporter Human Umbilical Vein Endothelial Cells Genetics Animals Guanine Nucleotide Exchange Factors Humans RNA Small Interfering Molecular Biology Zebrafish Gene knockdown Chemistry Endothelial Cells Cell migration Zebrafish Proteins Brefeldin A Cell biology Vesicular transport protein Endothelial stem cell 030104 developmental biology Gene Knockdown Techniques ADP-Ribosylation Factor 1 RNA Interference Guanine nucleotide exchange factor CRISPR-Cas Systems 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | The FASEB Journal. 33:9959-9973 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.201900342rr |
| Popis: | VEGF stimulates the formation of new blood vessels by inducing endothelial cell (EC) proliferation and migration. Brefeldin A (BFA)-inhibited guanine nucleotide-exchange protein (BIG)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 (CRISPR)/CRISPR-associated protein 9 (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. |
| Databáze: | OpenAIRE |
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