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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2001-5-24
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pubmed:abstractText |
Endothelin-1 (ET-1) has been implicated in the pathogenesis of renal inflammation. This study investigated the mechanisms underlying the synergistic upregulation of preproET-1 gene expression in human mesangial cells after co-stimulation with thrombin and tumor necrosis factor alpha (TNFalpha). Whereas thrombin induced a moderate upregulation of preproET-1 mRNA, co-stimulation with TNFalpha resulted in a strong and protracted upregulation of this mRNA species. Thrombin+TNFalpha-induced upregulation of preproET-1 expression was found to require p38 mitogen-activated protein kinase and protein kinases C, whereas activation of extracellular signal-regulated kinase, c-Jun-N-terminal kinase, or intracellular Ca(2+) release were not required. Actinomycin D chase experiments suggested that enhanced stability of preproET-1 mRNA did not account for the increase in transcript levels. PreproET-1 promoter analysis demonstrated that the 5'-flanking region of preproET-1 encompassed positive regulatory elements engaged by thrombin. Negative modulation of thrombin-induced activation exerted by the distal 5' portion of preproET-1 promoter (-4.4 kbp to 204 bp) was overcome by co-stimulation with TNFalpha, providing a possible mechanism underlying the synergistic upregulation of preproET-1 expression by these two agonists. In conclusion, human mesangial cell expression of preproET-1 may be increased potently in the presence of two common proinflammatory mediators, thereby providing a potential mechanism for ET-1 production in inflammatory renal disease.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Chloramphenicol O-Acetyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 11,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombin,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1046-6673
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1137-50
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11373337-Animals,
pubmed-meshheading:11373337-Blotting, Northern,
pubmed-meshheading:11373337-Calcium,
pubmed-meshheading:11373337-Cells, Cultured,
pubmed-meshheading:11373337-Chloramphenicol O-Acetyltransferase,
pubmed-meshheading:11373337-Endothelins,
pubmed-meshheading:11373337-Endothelium, Vascular,
pubmed-meshheading:11373337-Female,
pubmed-meshheading:11373337-Gene Expression Regulation,
pubmed-meshheading:11373337-Genetic Vectors,
pubmed-meshheading:11373337-Glomerular Mesangium,
pubmed-meshheading:11373337-Humans,
pubmed-meshheading:11373337-Male,
pubmed-meshheading:11373337-Mitogen-Activated Protein Kinase 11,
pubmed-meshheading:11373337-Mitogen-Activated Protein Kinases,
pubmed-meshheading:11373337-Protein Kinase C,
pubmed-meshheading:11373337-Protein-Tyrosine Kinases,
pubmed-meshheading:11373337-RNA, Messenger,
pubmed-meshheading:11373337-Rats,
pubmed-meshheading:11373337-Rats, Sprague-Dawley,
pubmed-meshheading:11373337-Thrombin,
pubmed-meshheading:11373337-Transfection,
pubmed-meshheading:11373337-Tumor Necrosis Factor-alpha,
pubmed-meshheading:11373337-Up-Regulation
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pubmed:year |
2001
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pubmed:articleTitle |
PreproEndothelin-1 expression in human mesangial cells: evidence for a p38 mitogen-activated protein kinase/protein kinases-C-dependent mechanism.
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pubmed:affiliation |
Medical College of Wisconsin, Milwaukee, Wisconsin 53226-0509, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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