Linked Life Data

14764443

Source:http://linkedlifedata.com/resource/pubmed/id/14764443

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-7-12
pubmed:abstractText
Extracellular nucleotides regulate a variety of cellular activities, including proliferation of fibrogenic cells outside of the liver. However, the expression of receptors for extracellular nucleotides in hepatic stellate cells (HSC) is unknown. Thus our aims were to investigate the expression of mediators of nucleotide signaling in HSC and to determine whether extracellular nucleotides regulate HSC function. Confocal video microscopy was used to observe nucleotide-induced changes in cytosolic Ca(2+) (Ca(i)(2+)) in live HSC. P2Y receptor subtype expression and ectonucleotidase expression in quiescent and activated HSC were determined using RT-PCR, Northern blot, immunoblot, and confocal immunofluorescence. Functional ectonucleotidase activity was assessed using a colorimetric method. Nucleotide-sensitive procollagen-1 mRNA expression in activated HSC was assessed using real-time RT-PCR. Extracellular ATP increased Ca(i)(2+) in HSC; this was inhibited by the P2 receptor inhibitor suramin. Quiescent HSC expressed the P2Y subtypes P2Y(2) and P2Y(4) and were activated by ATP and UTP, whereas activated HSC expressed the P2Y subtype P2Y(6) and were activated by UDP and ATP. Activated but not quiescent HSC expressed the ectonucleotidase nucleoside triphosphate diphosphohydrolase 2, extracellular UDP tripled procollagen-1 mRNA expression in activated HSC, and this was inhibited by the P2Y receptor inhibitor suramin. HSC express functional P2Y receptors and switch the expression of P2Y receptor subtypes on activation. Moreover, HSC differentially regulate nucleoside triphosphate diphosphohydrolase expression after activation. Because activation of P2Y receptors in activated HSC regulates procollagen-1 transcription, P2Y receptors may be an attractive target to prevent or treat liver fibrosis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate, http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Collagen Type I, http://linkedlifedata.com/resource/pubmed/chemical/Nucleoside-Triphosphatase, http://linkedlifedata.com/resource/pubmed/chemical/Nucleotidases, http://linkedlifedata.com/resource/pubmed/chemical/P2ry2 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2Y2, http://linkedlifedata.com/resource/pubmed/chemical/Uridine Diphosphate, http://linkedlifedata.com/resource/pubmed/chemical/Uridine Triphosphate, http://linkedlifedata.com/resource/pubmed/chemical/purinoceptor P2Y4, http://linkedlifedata.com/resource/pubmed/chemical/purinoceptor P2Y6
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0193-1857
pubmed:author
pubmed:issnType
Print
pubmed:volume
287
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G417-24
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Expression of P2Y nucleotide receptors and ectonucleotidases in quiescent and activated rat hepatic stellate cells.
pubmed:affiliation
Yale Univ. School of Medicine, Section of Digestive Diseases, 333 Cedar St. LMP 1080, New Haven, CT 06520, USA. jonathan.dranoff@yale.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't