Linked Life Data

19577003

Source:http://linkedlifedata.com/resource/pubmed/id/19577003

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-10-19
pubmed:abstractText
Diabetes mellitus is associated with vascular complications including an impairment of vascular function and alterations in the reactivity of blood vessels to vasoactive hormones. However, the signaling mechanisms leading to vascular dysfunction in diabetes are not fully understood. This microarray-based study was designed to identify differential gene expression between the normal and diabetic mesenteric vasculature and to investigate the effect of inhibiting epidermal growth factor receptor (EGFR) signaling on global gene expression in the mesenteric bed of streptozotocin (STZ)-induced diabetic rats. Transcriptome analysis was performed in triplicate using oligonucleotide microarrays housing 10,000 rat genes on the mesenteric bed of normal, diabetic, and diabetic rats treated with AG1478, a selective inhibitor of EGFR. Four weeks of diabetes led to a profound alteration in gene expression within the mesenteric bed with 1167 of the 3074 annotated genes being up-regulated and 141 genes down-regulated by at least 2-fold. The up-regulated gene ontologies included receptor tyrosine kinases, G-protein coupled receptors and ion channel activity. In particular, significant overexpressions of colipase, phospholipase A2, carboxypeptidases, and receptor tyrosine kinases such as EGFR, erbB2 and fibroblast growth factor receptor were observed in diabetes mesenteric vasculature. A 4-week intraperitoneal treatment of diabetic animals with AG1478 (1.2 mg/kg/alt diem) beginning on the same day as STZ injection prevented up-regulation of the majority (approximately 95%) of the genes associated with STZ diabetes including those apparently "unrelated" to the known EGFR pathway without correction of hyperglycemia. These results suggest that activation of EGFR signaling is a key initiating step that leads to induction of multiple signaling pathways in the development of diabetes-induced vascular dysfunction. Thus, therapeutic targeting of EGFR may represent a novel strategy for the prevention and/or treatment of vascular dysfunction in diabetes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1879-3649
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
236-45
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Early inhibition of EGFR signaling prevents diabetes-induced up-regulation of multiple gene pathways in the mesenteric vasculature.
pubmed:affiliation
Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Safat, Kuwait. ibenter@hsc.edu.kw
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't