Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-9-6
pubmed:abstractText
The effects of VEGF on endothelial cells are mediated by different intracellular signaling cascades (e.g., Erk1/2, Akt, Src). VEGF plays a recently recognized role in ulcerative colitis (UC) pathogenesis, mostly by increasing vascular permeability and promoting the infiltration of inflammatory cells. We hypothesized that the excessive activation of signal transduction pathways, which is responsible for VEGF/VEGFR-2-mediated endothelial permeability (Src, Akt), is a new element in the pathogenesis of chronic UC. We demonstrated increased expression of pro-angiogenic growth factor VEGF and its receptor VEGFR-2 in colonic tissue during acute 6% iodoacetamide-induced UC in rats and chronic spontaneously developed UC in IL-10 knockout mice (IL-10 KO). Development of acute 6% iodoacetamide-induced UC in rats was accompanied by activation of Erk1/2 and Src kinase, while expression of total proteins Erk1/2 and Src was unchanged. During chronic colitis phosphorylation (i.e., activation) of Erk1/2 was significantly decreased in IL-10 KO mice vs. wild-type mice. Levels of total Erk1/2 proteins were unchanged, but the expression of total Src protein as well as its phosphorylated form was significantly increased in IL-10 KO vs. wild-type mice. There were no changes in total Akt proteins, while levels of activated Akt (pAkt) were slightly increased in IL-10 KO vs. wild-type mice. We conclude that VEGF/VEGFR-2-associated signal transduction pathways, that mediate increased vascular permeability (Src, Akt), might play a central role in perpetuation of chronic experimental UC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1090-2104
pubmed:author
pubmed:copyrightInfo
Published by Elsevier Inc.
pubmed:issnType
Electronic
pubmed:day
3
pubmed:volume
399
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
613-6
pubmed:meshHeading
pubmed-meshheading:20682292-Animals, pubmed-meshheading:20682292-Capillary Permeability, pubmed-meshheading:20682292-Colitis, Ulcerative, pubmed-meshheading:20682292-Colon, pubmed-meshheading:20682292-Interleukin-10, pubmed-meshheading:20682292-Iodoacetamide, pubmed-meshheading:20682292-Mice, pubmed-meshheading:20682292-Mice, Knockout, pubmed-meshheading:20682292-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:20682292-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:20682292-Phosphorylation, pubmed-meshheading:20682292-Proto-Oncogene Proteins c-akt, pubmed-meshheading:20682292-Rats, pubmed-meshheading:20682292-Rats, Sprague-Dawley, pubmed-meshheading:20682292-Signal Transduction, pubmed-meshheading:20682292-Vascular Endothelial Growth Factor A, pubmed-meshheading:20682292-Vascular Endothelial Growth Factor Receptor-2, pubmed-meshheading:20682292-src-Family Kinases
pubmed:year
2010
pubmed:articleTitle
New molecular mechanisms of the unexpectedly complex role of VEGF in ulcerative colitis.
pubmed:affiliation
Diagnostic & Molecular Medicine Health Care Group, VA Medical Center, and Departments of Pathology and Pharmacology, University of California-Irvine, Long Beach, CA 90822, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.