Activation of VEGF and Ras genes in gastric mucosa during angiogenic response to ethanol injury.
Our previous studies demonstrated that ethanol injury triggers the angiogenic response in gastric mucosa bordering necrosis. The present study was aimed to determine whether vascular endothelial growth factor (VEGF) (a potent angiogenic peptide selectively acting on endothelial cells) and Ras (a mediator of cell proliferation and a putative regulator of VEGF expression) are involved in gastric angiogenesis after ethanol injury. We studied the angiogenic response and expression of VEGF and Ras in gastric mucosa after ethanol injury. Ethanol damage triggered 1) angiogenesis in the gastric mucosa bordering necrosis, 2) significant increases in VEGF mRNA and protein expression, and 3) significant increases in the expression of Ki-ras mRNA and Ras proteins. Neutralizing anti-VEGF antibody significantly reduced (by greater than threefold) the angiogenic response to ethanol-induced injury. Moreover, mevastatin, an inhibitor of Ras activation, completely blocked the induction of VEGF expression in cultured primary endothelial cells. Because, in other tissues, VEGF is one of the most potent angiogenic factors and VEGF expression is dependent on Ras, our data indicate that Ras and VEGF are involved in gastric mucosal angiogenesis after ethanol injury.
Jones
M K
MK
Veterans Affairs Medical Center, Long Beach, CA, 90822, USA.
Itani
R M
RM
Wang
H
H
Tomikawa
M
M
Sarfeh
I J
IJ
Szabo
S
S
Tarnawski
A S
AS
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D011905:Genes, ras / Q000235:genetics*; D008222:Lymphokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology
D000906:Antibodies; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000431:Ethanol; D018631:ras Proteins