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PMID: 2820711 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Transforming growth factor beta modulates the expression of collagenase and metalloproteinase inhibitor.

The EMBO journal ·Vol. 6 ·No. 7 ·1987-07-00 ·Pages 1899-904

Edwards DR, Murphy G, Reynolds JJ, Whitham SE, Docherty AJ, Angel P, Heath JK

Abstract

Exposure of quiescent MRC-5 human fibroblasts to growth factors such as epidermal growth factor, basic fibroblast growth factor or embryonal carcinoma-derived growth factor resulted in the induction of mRNA transcripts encoding the metalloproteinases collagenase and stromelysin and the specific metalloproteinase inhibitor TIMP, whilst expression of collagen and fibronectin was relatively unaffected. Exposure of quiescent cells to growth factors in the presence of transforming growth factor beta (TGF-beta) resulted in inhibition of collagenase induction and a synergistic increase in TIMP expression. TGF-beta alone did not significantly induce metalloproteinase or TIMP expression. These effects on mRNA transcripts were reflected in increased secretion of TIMP protein and collagenase activity. Nuclear run-off analysis of growth factor-induced transcription revealed that the TGF-beta modulation of TIMP and collagenase expression was due to transcriptional mechanisms. The observations suggest that TGF-beta exerts a selective effect on extracellular matrix deposition by modulating the action of other growth factors on metalloproteinase and TIMP expression.

MeSH Terms
Cell Line Gene Expression Regulation/drug effects Genes/drug effects Growth Substances/pharmacology Humans Metalloendopeptidases/antagonists & inhibitors,genetics Microbial Collagenase/genetics Peptides/pharmacology Protein Biosynthesis RNA, Messenger/genetics Transcription, Genetic/drug effects Transforming Growth Factors
Chemicals
Growth Substances Peptides RNA, Messenger Transforming Growth Factors Metalloendopeptidases Microbial Collagenase
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Edwards D R
Department of Biochemistry, University of Oxford, UK.
Murphy G
Reynolds J J
Whitham S E
Docherty A J
Angel P
Heath J K
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1987-07-00
Pages
1899-904
Language
English
Region
England
NLM ID
8208664
PMCID
PMC553574
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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