Linked Life Data

10820165

Source:http://linkedlifedata.com/resource/pubmed/id/10820165

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2000-8-10
pubmed:abstractText
Interstitial fibrin deposition is a common histologic feature of tubulointerstitial diseases, which suggests that the coagulation system is activated. Thrombin, generated during the activation of the coagulation cascade, is a powerful activating factor for different cell types. Although proximal tubular cells are potential targets for this coagulation factor, no information is available on the effect of thrombin on these cells. Thus, the expression of protease-activated receptor-1 (PAR-1), the main thrombin receptor, was investigated in human proximal tubular cells (hPTC) in vivo and in vitro. A diffuse expression of PAR-1 was observed by immunohistochemistry along the basolateral membrane of PTC in normal human kidney. This observation was confirmed in vitro in cultured hPTC. Because tubular damage and monocyte infiltration are two hallmarks of tubulointerstitial injury, the effect of thrombin on DNA synthesis and monocyte chemotactic peptide-1 (MCP-1) gene and protein expression was evaluated in cultured hPTC. Thrombin induced a significant and dose-dependent increase in thymidine uptake and a striking upregulation of MCP-1 mRNA expression and protein release into the supernatant. Although PAR-1 is a G protein-coupled receptor, its activation in hPTC, as in other cell systems, resulted in a transient increase in cellular levels of tyrosine-phosphorylated proteins. An increased level of tyrosine-phosphorylated c-src suggested the activation of this cytoplasmic tyrosine kinase in response to thrombin and its potential role in thrombin-induced protein-tyrosine phosphorylation. Interestingly, thrombin-induced DNA synthesis and MCP-1 gene expression were completely blocked by genistein, a specific tyrosine kinase inhibitor, but not by its inactive analogue daidzein, demonstrating a central role for tyrosine kinase activation in the thrombin effects on hPTC. Moreover, the specific src inhibitor PP1 abolished the thrombin effect on DNA synthesis. In conclusion, thrombin might represent a powerful regenerative and proinflammatory stimulus for hPTC in acute and chronic tubulointerstitial diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1046-6673
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1016-25
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10820165-Analysis of Variance, pubmed-meshheading:10820165-Antibodies, Monoclonal, pubmed-meshheading:10820165-Cell Line, pubmed-meshheading:10820165-Chemokine CCL2, pubmed-meshheading:10820165-DNA, pubmed-meshheading:10820165-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:10820165-Gene Expression, pubmed-meshheading:10820165-Humans, pubmed-meshheading:10820165-Immunochemistry, pubmed-meshheading:10820165-Inflammation, pubmed-meshheading:10820165-Kidney Tubules, Proximal, pubmed-meshheading:10820165-Molecular Probe Techniques, pubmed-meshheading:10820165-Phosphorylation, pubmed-meshheading:10820165-RNA, pubmed-meshheading:10820165-RNA, Messenger, pubmed-meshheading:10820165-Receptor, PAR-1, pubmed-meshheading:10820165-Receptors, Thrombin, pubmed-meshheading:10820165-Regeneration, pubmed-meshheading:10820165-Thrombin, pubmed-meshheading:10820165-Up-Regulation
pubmed:year
2000
pubmed:articleTitle
Regenerative and proinflammatory effects of thrombin on human proximal tubular cells.
pubmed:affiliation
Division of Nephrology/Department of Emergency and Transplantation, University of Bari, Italy. g.grandaliano@nephro.uniba.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't