Linked Life Data

14500687

Source:http://linkedlifedata.com/resource/pubmed/id/14500687

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2003-9-22
pubmed:abstractText
Transforming growth factor-beta stimulates the production of the extracellular matrix, whereas TNF-alpha has antifibrotic activity. Understanding the molecular mechanism underlying the antagonistic activities of TNF-alpha against TGF-beta is critical in the context of tissue repair and maintenance of tissue homeostasis. In the present study, we demonstrated a novel mechanism by which TNF-alpha blocks TGF-beta-induced gene and signaling pathways in human dermal fibroblasts. We showed that TNF-alpha prevents TGF-beta-induced gene trans activation, such as alpha2(I) collagen or tissue inhibitor of metalloproteinases 1, and TGF-beta signaling pathways, such as Smad3, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinases, without inducing levels of inhibitory Smad7 in human dermal fibroblasts. TNF-alpha down-regulates the expression of type II TGF-beta receptor (TbetaRII) proteins, but not type I TGF-beta receptor (TbetaRI), in human dermal fibroblasts. However, neither TbetaRII mRNA nor TbetaRII promoter activity was decreased by TNF-alpha. TNF-alpha-mediated decrease of TbetaRII protein expression was not inhibited by the treatment of fibroblasts with either a selective inhibitor of I-kappaB-alpha phosphorylation, BAY 11-7082, or a mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor, PD98059. Calpain inhibitor I (ALLN), a protease inhibitor, inhibits TNF-alpha-mediated down-regulation of TbetaRII. We found that TNF-alpha triggered down-regulation of TbetaRII, leading to desensitization of human dermal fibroblasts toward TGF-beta. Furthermore, these events seemed to cause a dramatic down-regulation of alpha2(I) collagen and tissue inhibitor of metalloproteinases 1 in systemic sclerosis fibroblasts. These results indicated that TNF-alpha impaired the response of the cells to TGF-beta by regulating the turnover of TbetaRII.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
171
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3855-62
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:14500687-Cells, Cultured, pubmed-meshheading:14500687-DNA-Binding Proteins, pubmed-meshheading:14500687-Down-Regulation, pubmed-meshheading:14500687-Extracellular Matrix, pubmed-meshheading:14500687-Fibroblasts, pubmed-meshheading:14500687-Gene Expression Regulation, pubmed-meshheading:14500687-Humans, pubmed-meshheading:14500687-Protein-Serine-Threonine Kinases, pubmed-meshheading:14500687-Receptors, Transforming Growth Factor beta, pubmed-meshheading:14500687-Scleroderma, Systemic, pubmed-meshheading:14500687-Signal Transduction, pubmed-meshheading:14500687-Skin Physiological Phenomena, pubmed-meshheading:14500687-Smad7 Protein, pubmed-meshheading:14500687-Trans-Activators, pubmed-meshheading:14500687-Transforming Growth Factor beta, pubmed-meshheading:14500687-Tumor Necrosis Factor-alpha
pubmed:year
2003
pubmed:articleTitle
Antagonistic effects of TNF-alpha on TGF-beta signaling through down-regulation of TGF-beta receptor type II in human dermal fibroblasts.
pubmed:affiliation
Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't