Linked Life Data

16522324

Source:http://linkedlifedata.com/resource/pubmed/id/16522324

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-6-19
pubmed:abstractText
Angiotensin II (Ang II) stimulation has been shown to regulate proliferation of skin fibroblasts and production of extracellular matrix, which are very important process in skin wound healing and scarring; however, the signaling pathways involved in this process, especially in humans, are less explored. In the present study, we used skin fibroblasts of human hypertrophic scar, which expressed both AT1 and AT2 receptors, and observed that Ang II increased Akt phosphorylation and phosphoinositide 3 kinase (PI 3-K) activity. In addition, the Ang II-induced Akt phosphorylation was blocked by wortmannin, a PI 3-K inhibitor. This Ang II-activated PI 3-K/Akt cascade was markedly inhibited by valsartan, an AT(1) receptor-specific blocker, whereas it was enhanced by PD123319, an AT(2) receptor antagonist. On the other hand, the Ang II- or EGF-induced activation of PI 3-K/Akt was strongly attenuated by AG1478, an inhibitor of epidermal growth factor (EGF) receptor kinase. Moreover, Ang II stimulated tyrosine phosphorylation of EGF receptor and p85alpha subunit of PI 3-K accompanied by an increase in their association, which was inhibited by valsartan, and enhanced by PD123319. The Ang II-induced transactivation of EGF receptor resulted in activation of extracellular signal-regulated kinase (ERK) that was also inhibited by valsartan, and enhanced by PD123319. Taken together, our results showed that AT(1) receptor-mediated activation of PI 3-K/Akt cascades occurs at least partially via the transactivation of EGF receptor, which is under a negative control by AT(2) receptor in hypertrophic scar fibroblasts. These findings contribute to understanding the molecular mechanism of human hypertrophic scar formation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0024-3205
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
79
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
475-83
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16522324-Angiotensin II, pubmed-meshheading:16522324-Cells, Cultured, pubmed-meshheading:16522324-Cicatrix, Hypertrophic, pubmed-meshheading:16522324-Enzyme Activation, pubmed-meshheading:16522324-Fibroblasts, pubmed-meshheading:16522324-Humans, pubmed-meshheading:16522324-Phosphatidylinositol 3-Kinases, pubmed-meshheading:16522324-Phosphorylation, pubmed-meshheading:16522324-Phosphotransferases, pubmed-meshheading:16522324-Proto-Oncogene Proteins c-akt, pubmed-meshheading:16522324-RNA, Messenger, pubmed-meshheading:16522324-Receptor, Angiotensin, Type 1, pubmed-meshheading:16522324-Receptor, Angiotensin, Type 2, pubmed-meshheading:16522324-Receptor, Epidermal Growth Factor, pubmed-meshheading:16522324-Receptor Cross-Talk, pubmed-meshheading:16522324-Receptors, Angiotensin, pubmed-meshheading:16522324-Signal Transduction, pubmed-meshheading:16522324-Skin, pubmed-meshheading:16522324-Transcriptional Activation
pubmed:year
2006
pubmed:articleTitle
Angiotensin II regulates phosphoinositide 3 kinase/Akt cascade via a negative crosstalk between AT1 and AT2 receptors in skin fibroblasts of human hypertrophic scars.
pubmed:affiliation
Department of Plastic Surgery, Guangzhou Liuhuaqiao Hospital, Liuhua road 111, Guangzhou, Guangdong Province 510010, PR China. liuhongwei0521@hotmail.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't