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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2005-4-27
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pubmed:abstractText |
The extracellular matrix (ECM) glycoprotein thrombospondin-1 (TSP-1) has been reported to activate the latent complex of transforming growth factor-beta (TGF-beta), the major effects of which in mesenchymal cells is stimulation of the synthesis of ECM. Previous reports suggested the involvement of an autocrine TGF-beta loop in the pathogenesis of scleroderma. In this study, we examined whether TSP-1 plays a role in maintaining the autocrine TGF-beta loop in scleroderma. TSP-1 expression was increased in scleroderma patients compared with in healthy controls in vivo and in vitro. TGF-beta blocking antibody or TGF-beta1 antisense oligonucleotide markedly reduced the up-regulated TSP-1 expression in scleroderma fibroblasts but had little effect on normal fibroblasts. The expression of TSP-1 is up-regulated in scleroderma fibroblasts, possibly at the post-transcriptional level just like in normal fibroblasts stimulated with exogenous TGF-beta1. TSP-1 blocking peptide or antisense oligonucleotide had an inhibitory effect on the up-regulated alpha2I collagen and phosopho-Smad3 levels in scleroderma fibroblasts but had little effects on normal fibroblasts. The transient overexpression of TSP-1 up-regulated alpha2I collagen and phospho-Smad3 levels in normal fibroblasts but had no major effect on scleroderma fibroblasts. Furthermore, these effects of transiently overexpressed TSP-1, which possibly occurred via the activation of latent TGF-beta1, were abolished by the TGF-beta1 antisense oligonucleotide. These results indicate that the constitutive overexpression of TSP-1 may play an important role in autocrine TGF-beta signaling and accumulation of ECM in scleroderma fibroblasts.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-10082755,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-10224129,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-10487979,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-10880440,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-11114293,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-11152469,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-11229480,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-11274231,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-11642546,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-11823524,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-12465152,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-12465153,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-12482908,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-12670720,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-12847691,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-12888575,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-12937160,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-15153536,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-1697606,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-2161232,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-2177343,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-2261003,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-2406813,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-2544587,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-2702049,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-2719731,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-3800922,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-4430718,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-6833837,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-7229432,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-7669547,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-7706271,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-7791754,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-7929414,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-8349738,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-8900150,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-90059,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-9150447,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-9304800,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-9424086,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-9461090,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-9609460,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-9657149,
http://linkedlifedata.com/resource/pubmed/commentcorrection/15855645-9856839
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Collagen,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen Type I,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/TGFB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombospondin 1,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1,
http://linkedlifedata.com/resource/pubmed/chemical/alpha 2(I) collagen
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0002-9440
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
166
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1451-63
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:15855645-Humans,
pubmed-meshheading:15855645-Skin,
pubmed-meshheading:15855645-Scleroderma, Systemic,
pubmed-meshheading:15855645-Collagen,
pubmed-meshheading:15855645-Phosphorylation,
pubmed-meshheading:15855645-Fibroblasts,
pubmed-meshheading:15855645-Cells, Cultured,
pubmed-meshheading:15855645-RNA, Messenger,
pubmed-meshheading:15855645-Case-Control Studies,
pubmed-meshheading:15855645-Signal Transduction,
pubmed-meshheading:15855645-Promoter Regions, Genetic,
pubmed-meshheading:15855645-DNA-Binding Proteins
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