Premium
ADAM‐17: a Central Regulator of Angiogenesis
Author(s) -
Gooz Pal,
Gooz Monika,
Hoffman Stanley
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a30-c
Subject(s) - angiogenesis , matrigel , regulator , vascular endothelial growth factor , microbiology and biotechnology , in vitro , chemistry , mapk/erk pathway , in vivo , biology , signal transduction , cancer research , vegf receptors , biochemistry , genetics , gene
We have recently identified ADAM‐17 as a regulator of angiogenesis and the angiogenic switch induced by VEGF. The importance of ADAM‐17 in angiogenesis was suggested by the observations that the pro‐angiogenic growth factor VEGF induces ADAM‐17 expression and catalytic activity. To perturb the expression of ADAM‐17 in vitro and in vivo, we developed lentivirus that encode an shRNA that almost completely blocks ADAM‐17 expression in HUVECs. These ADAM‐17‐negative HUVECs could not participate in VEGF‐induced angiogenesis in vitro: 1) capillary‐like networks that form when control HUVECs are cultured on Matrigel are unstable when ADAM‐17‐negative HUVECs are used, 2) the VEGF‐induced invasion of these cells through Matrigel is inhibited by 88 % whereas baseline invasion is unaffected, 3) VEGF‐dependent vessel formation in a three‐dimensional model in which HUVECs are co‐cultured with fibroblasts or with pericytes is blocked when ADAM‐17‐negative HUVECs are used, and 4) VEGF‐induced signaling involving ERK activation or MMP‐2 activation is blocked in ADAM‐17‐negative HUVECs. This work was supported by SC COBRE for Cardiovascular Disease NIH NCCR P20 RR016434 to P.G.and NIH 1K01 DK070054‐01 to M.G.