Transforming growth factor-beta is a strong and fast acting positive regulator of the level of type-1 plasminogen activator inhibitor mRNA in WI-38 human lung fibroblasts.

L. R. Lund, A. Riccio, P. A. Andreasen, L. S. Nielsen, P. Kristensen, Marikki Laiho, O. Saksela, F. Blasi, K. Danø

Research output: Contribution to journalArticle

Abstract

We have studied the mechanism of a transforming growth factor-beta (TGF-beta)-stimulated production of type-1 plasminogen activator inhibitor (PAI-1) in WI-38 human lung fibroblasts. TGF-beta causes an early increase in the PAI-1 mRNA level which reaches a maximal 50-fold enhancement after 8 h. Blocking of protein synthesis with cycloheximide causes an equally strong increase in the level of PAI-1 mRNA. Quantitative studies of the effect of TGF-beta on PAI-1 protein levels in cell extracts and culture media by using monoclonal antibodies are consistent with the effect on PAI-1 mRNA. The results suggest a primary effect of TGF-beta on PAI-1 gene transcription, and also suggest the possibility that the transcription of this gene in non-induced cells may be suppressed by a short-lived negatively regulating protein. Urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators are decreased in the culture media of TGF-beta-treated cells concomitantly with the increase in PAI-1 accumulation. These findings show that a primary and important biological effect of TGF-beta may be an overall decreased extracellular proteolytic activity, and give an insight into the molecular mechanisms underlying TGF-beta action at the genetic level.

Original languageEnglish (US)
Pages (from-to)1281-1286
Number of pages6
JournalThe EMBO journal
Volume6
Issue number5
StatePublished - May 1987
Externally publishedYes

Fingerprint

Plasminogen Activator Inhibitor 1
Fibroblasts
Transforming Growth Factor beta
Lung
Messenger RNA
Transcription
Culture Media
Genes
Proteins
Plasminogen Activators
Urokinase-Type Plasminogen Activator
Cycloheximide
Cell Extracts
Monoclonal Antibodies
Cells
Tissue
Cell Culture Techniques

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

Transforming growth factor-beta is a strong and fast acting positive regulator of the level of type-1 plasminogen activator inhibitor mRNA in WI-38 human lung fibroblasts. / Lund, L. R.; Riccio, A.; Andreasen, P. A.; Nielsen, L. S.; Kristensen, P.; Laiho, Marikki; Saksela, O.; Blasi, F.; Danø, K.

In: The EMBO journal, Vol. 6, No. 5, 05.1987, p. 1281-1286.

Research output: Contribution to journalArticle

Lund, LR, Riccio, A, Andreasen, PA, Nielsen, LS, Kristensen, P, Laiho, M, Saksela, O, Blasi, F & Danø, K 1987, 'Transforming growth factor-beta is a strong and fast acting positive regulator of the level of type-1 plasminogen activator inhibitor mRNA in WI-38 human lung fibroblasts.', The EMBO journal, vol. 6, no. 5, pp. 1281-1286.
Lund, L. R. ; Riccio, A. ; Andreasen, P. A. ; Nielsen, L. S. ; Kristensen, P. ; Laiho, Marikki ; Saksela, O. ; Blasi, F. ; Danø, K. / Transforming growth factor-beta is a strong and fast acting positive regulator of the level of type-1 plasminogen activator inhibitor mRNA in WI-38 human lung fibroblasts. In: The EMBO journal. 1987 ; Vol. 6, No. 5. pp. 1281-1286.
@article{5c364c6ce29240aa88e1dc80eb7dd25b,
title = "Transforming growth factor-beta is a strong and fast acting positive regulator of the level of type-1 plasminogen activator inhibitor mRNA in WI-38 human lung fibroblasts.",
abstract = "We have studied the mechanism of a transforming growth factor-beta (TGF-beta)-stimulated production of type-1 plasminogen activator inhibitor (PAI-1) in WI-38 human lung fibroblasts. TGF-beta causes an early increase in the PAI-1 mRNA level which reaches a maximal 50-fold enhancement after 8 h. Blocking of protein synthesis with cycloheximide causes an equally strong increase in the level of PAI-1 mRNA. Quantitative studies of the effect of TGF-beta on PAI-1 protein levels in cell extracts and culture media by using monoclonal antibodies are consistent with the effect on PAI-1 mRNA. The results suggest a primary effect of TGF-beta on PAI-1 gene transcription, and also suggest the possibility that the transcription of this gene in non-induced cells may be suppressed by a short-lived negatively regulating protein. Urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators are decreased in the culture media of TGF-beta-treated cells concomitantly with the increase in PAI-1 accumulation. These findings show that a primary and important biological effect of TGF-beta may be an overall decreased extracellular proteolytic activity, and give an insight into the molecular mechanisms underlying TGF-beta action at the genetic level.",
author = "Lund, {L. R.} and A. Riccio and Andreasen, {P. A.} and Nielsen, {L. S.} and P. Kristensen and Marikki Laiho and O. Saksela and F. Blasi and K. Dan{\o}",
year = "1987",
month = "5",
language = "English (US)",
volume = "6",
pages = "1281--1286",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Transforming growth factor-beta is a strong and fast acting positive regulator of the level of type-1 plasminogen activator inhibitor mRNA in WI-38 human lung fibroblasts.

AU - Lund, L. R.

AU - Riccio, A.

AU - Andreasen, P. A.

AU - Nielsen, L. S.

AU - Kristensen, P.

AU - Laiho, Marikki

AU - Saksela, O.

AU - Blasi, F.

AU - Danø, K.

PY - 1987/5

Y1 - 1987/5

N2 - We have studied the mechanism of a transforming growth factor-beta (TGF-beta)-stimulated production of type-1 plasminogen activator inhibitor (PAI-1) in WI-38 human lung fibroblasts. TGF-beta causes an early increase in the PAI-1 mRNA level which reaches a maximal 50-fold enhancement after 8 h. Blocking of protein synthesis with cycloheximide causes an equally strong increase in the level of PAI-1 mRNA. Quantitative studies of the effect of TGF-beta on PAI-1 protein levels in cell extracts and culture media by using monoclonal antibodies are consistent with the effect on PAI-1 mRNA. The results suggest a primary effect of TGF-beta on PAI-1 gene transcription, and also suggest the possibility that the transcription of this gene in non-induced cells may be suppressed by a short-lived negatively regulating protein. Urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators are decreased in the culture media of TGF-beta-treated cells concomitantly with the increase in PAI-1 accumulation. These findings show that a primary and important biological effect of TGF-beta may be an overall decreased extracellular proteolytic activity, and give an insight into the molecular mechanisms underlying TGF-beta action at the genetic level.

AB - We have studied the mechanism of a transforming growth factor-beta (TGF-beta)-stimulated production of type-1 plasminogen activator inhibitor (PAI-1) in WI-38 human lung fibroblasts. TGF-beta causes an early increase in the PAI-1 mRNA level which reaches a maximal 50-fold enhancement after 8 h. Blocking of protein synthesis with cycloheximide causes an equally strong increase in the level of PAI-1 mRNA. Quantitative studies of the effect of TGF-beta on PAI-1 protein levels in cell extracts and culture media by using monoclonal antibodies are consistent with the effect on PAI-1 mRNA. The results suggest a primary effect of TGF-beta on PAI-1 gene transcription, and also suggest the possibility that the transcription of this gene in non-induced cells may be suppressed by a short-lived negatively regulating protein. Urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators are decreased in the culture media of TGF-beta-treated cells concomitantly with the increase in PAI-1 accumulation. These findings show that a primary and important biological effect of TGF-beta may be an overall decreased extracellular proteolytic activity, and give an insight into the molecular mechanisms underlying TGF-beta action at the genetic level.

UR - http://www.scopus.com/inward/record.url?scp=0023337921&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023337921&partnerID=8YFLogxK

M3 - Article

C2 - 3111844

AN - SCOPUS:0023337921

VL - 6

SP - 1281

EP - 1286

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 5

ER -