Linked Life Data

11278621

Source:http://linkedlifedata.com/resource/pubmed/id/11278621

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2001-6-11
pubmed:abstractText
Fibrosis is characterized by the excessive deposition of extracellular matrix (ECM), especially collagen. Because Ets factors are implicated in physiological and pathological ECM remodeling, the aim of this study was to investigate the role of Ets factors in collagen production. We demonstrate that the expression of collagenous proteins and collagen alpha2(I) (COL1A2) mRNA was inhibited following stable transfection of Fli-1 in dermal fibroblasts. Subsequent analysis of the COL1A2 promoter identified a critical Ets binding site that mediates Fli-1 inhibition. In contrast, Ets-1 stimulates COL1A2 promoter activity. In vitro binding assays demonstrate that both Fli-1 and Ets-1 form DNA-protein complexes with sequences present in COL1A2 promoter. Furthermore, Fli-1 binding to the COL1A2 is enhanced via Sp1-dependent interaction. Studies using Fli-1 dominant interference and DNA binding mutants indicate that Fli-1 inhibition is mediated by both direct (DNA binding) and indirect (via protein-protein interaction) mechanisms and that Sp1 is an important mediator of the Fli-1 function. Furthermore, experiments using the Gal4 system in the context of different cell types as well as experiments with the COL1A2 promoter in different cell lines demonstrate that the direction and magnitude of the effect of Fli-1 is promoter- and cell context-specific. We propose that Fli-1 inhibits COL1A2 promoter activity by competition with Ets-1. In addition, we postulate that another factor (co-repressor) may be required for maximal inhibition after recruitment to the Fli-1-Sp1 complex. We conclude that the ratio of Fli-1 to Ets-1 and the presence of co-regulatory proteins ultimately control ECM production in fibroblasts.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20839-48
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11278621-Base Sequence, pubmed-meshheading:11278621-Binding Sites, pubmed-meshheading:11278621-Cells, Cultured, pubmed-meshheading:11278621-Collagen, pubmed-meshheading:11278621-DNA-Binding Proteins, pubmed-meshheading:11278621-Fibroblasts, pubmed-meshheading:11278621-Gene Expression Regulation, pubmed-meshheading:11278621-Genes, Reporter, pubmed-meshheading:11278621-Humans, pubmed-meshheading:11278621-Infant, Newborn, pubmed-meshheading:11278621-Kinetics, pubmed-meshheading:11278621-Male, pubmed-meshheading:11278621-Molecular Sequence Data, pubmed-meshheading:11278621-Promoter Regions, Genetic, pubmed-meshheading:11278621-Protein Biosynthesis, pubmed-meshheading:11278621-Proto-Oncogene Protein c-fli-1, pubmed-meshheading:11278621-Proto-Oncogene Proteins, pubmed-meshheading:11278621-Recombinant Proteins, pubmed-meshheading:11278621-Skin, pubmed-meshheading:11278621-Sp1 Transcription Factor, pubmed-meshheading:11278621-Trans-Activators, pubmed-meshheading:11278621-Transcription, Genetic, pubmed-meshheading:11278621-Transfection
pubmed:year
2001
pubmed:articleTitle
Fli-1 inhibits collagen type I production in dermal fibroblasts via an Sp1-dependent pathway.
pubmed:affiliation
Department of Medicine, Division of Rheumatology, Medical University of South Carolina, Charleston, South Carolina 29401, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't