Regulation of mRNAs for type-1 plasminogen activator inhibitor, fibronectin, and type I procollagen by transforming growth factor-β. Divergent responses in lung fibroblasts and carcinoma cells

J. Keski-Oja, Rajendra Raghow, M. Sawdey, D. J. Loskutoff, Arnold Postlethwaite, Andrew Kang, H. L. Moses

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Abstract

Transforming growth factor-β (TGFβ) is a growth modulator which stimulates the growth of fibroblasts but acts as a strong growth inhibitor for cells of epithelial origin. TGFβ also influences the production of extracellular matrix proteins and of proteases and protease inhibitors by cultured cells. One important protease inhibitor whose production is affected rapidly by TGFβ is the type-1 plasminogen activator inhibitor (PAI-1). To investigate the relationships between PAI-1 and the extracellular matrix, we analyzed the regulation by TGFβ of PAI-1, fibronectin, and type I procollagen in malignant human lung carcinoma cells (A549) and in human lung fibroblasts (WI-38). The expression of the respective genes was examined by polypeptide analyses and by measurements of the steady-state levels of the corresponding mRNAs by Northern hybridization. The mRNA levels for PAI-1 were elevated rapidly by TGFβ in both cell lines. This induction occurred in the presence of cycloheximide and thus was not dependent on protein synthesis. In fact, the effects of TGFβ and cycloheximide on PAI-1 mRNA were additive. In contrast, the induction of fibronectin, β-actin, and type I procollagen (synthesized only in WI-38 cells) was abrogated by cycloheximide. In general, the effects of TGFβ on the steady-state levels of mRNAs for fibronectin, actin, and type I procollagen mRNA were similar in the two cell types. However, the production of PAI-1 mRNA in response to TGFβ differed in the two cell types, being transient (peak within 5 h) in the carcinoma cells and more persistent in fibroblasts. Thus, the major difference in TGFβ regulation of PAI-1 mRNA between lung fibroblasts and carcinoma cells was the duration of the effect. These results, together with previous data, suggest that PAI-1 and plasminogen activators may be regulated oppositely by TGFβ. We therefore propose a model for TGFβ in the regulation of extracellular proteolytic activity.

Original languageEnglish (US)
Pages (from-to)3111-3115
Number of pages5
JournalJournal of Biological Chemistry
Volume263
Issue number7
StatePublished - 1988
Externally publishedYes

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Plasminogen Activator Inhibitor 1
Transforming Growth Factors
Fibroblasts
Collagen Type I
Fibronectins
Cells
Carcinoma
Lung
Messenger RNA
Cycloheximide
Protease Inhibitors
Actins
Growth Inhibitors
Plasminogen Activators
Extracellular Matrix Proteins
Growth
Modulators
Extracellular Matrix
Cultured Cells
Peptide Hydrolases

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

@article{9a67072b0e434f7c95ec9b1a08454968,
title = "Regulation of mRNAs for type-1 plasminogen activator inhibitor, fibronectin, and type I procollagen by transforming growth factor-β. Divergent responses in lung fibroblasts and carcinoma cells",
abstract = "Transforming growth factor-β (TGFβ) is a growth modulator which stimulates the growth of fibroblasts but acts as a strong growth inhibitor for cells of epithelial origin. TGFβ also influences the production of extracellular matrix proteins and of proteases and protease inhibitors by cultured cells. One important protease inhibitor whose production is affected rapidly by TGFβ is the type-1 plasminogen activator inhibitor (PAI-1). To investigate the relationships between PAI-1 and the extracellular matrix, we analyzed the regulation by TGFβ of PAI-1, fibronectin, and type I procollagen in malignant human lung carcinoma cells (A549) and in human lung fibroblasts (WI-38). The expression of the respective genes was examined by polypeptide analyses and by measurements of the steady-state levels of the corresponding mRNAs by Northern hybridization. The mRNA levels for PAI-1 were elevated rapidly by TGFβ in both cell lines. This induction occurred in the presence of cycloheximide and thus was not dependent on protein synthesis. In fact, the effects of TGFβ and cycloheximide on PAI-1 mRNA were additive. In contrast, the induction of fibronectin, β-actin, and type I procollagen (synthesized only in WI-38 cells) was abrogated by cycloheximide. In general, the effects of TGFβ on the steady-state levels of mRNAs for fibronectin, actin, and type I procollagen mRNA were similar in the two cell types. However, the production of PAI-1 mRNA in response to TGFβ differed in the two cell types, being transient (peak within 5 h) in the carcinoma cells and more persistent in fibroblasts. Thus, the major difference in TGFβ regulation of PAI-1 mRNA between lung fibroblasts and carcinoma cells was the duration of the effect. These results, together with previous data, suggest that PAI-1 and plasminogen activators may be regulated oppositely by TGFβ. We therefore propose a model for TGFβ in the regulation of extracellular proteolytic activity.",
author = "J. Keski-Oja and Rajendra Raghow and M. Sawdey and Loskutoff, {D. J.} and Arnold Postlethwaite and Andrew Kang and Moses, {H. L.}",
year = "1988",
language = "English (US)",
volume = "263",
pages = "3111--3115",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
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TY - JOUR

T1 - Regulation of mRNAs for type-1 plasminogen activator inhibitor, fibronectin, and type I procollagen by transforming growth factor-β. Divergent responses in lung fibroblasts and carcinoma cells

AU - Keski-Oja, J.

AU - Raghow, Rajendra

AU - Sawdey, M.

AU - Loskutoff, D. J.

AU - Postlethwaite, Arnold

AU - Kang, Andrew

AU - Moses, H. L.

PY - 1988

Y1 - 1988

N2 - Transforming growth factor-β (TGFβ) is a growth modulator which stimulates the growth of fibroblasts but acts as a strong growth inhibitor for cells of epithelial origin. TGFβ also influences the production of extracellular matrix proteins and of proteases and protease inhibitors by cultured cells. One important protease inhibitor whose production is affected rapidly by TGFβ is the type-1 plasminogen activator inhibitor (PAI-1). To investigate the relationships between PAI-1 and the extracellular matrix, we analyzed the regulation by TGFβ of PAI-1, fibronectin, and type I procollagen in malignant human lung carcinoma cells (A549) and in human lung fibroblasts (WI-38). The expression of the respective genes was examined by polypeptide analyses and by measurements of the steady-state levels of the corresponding mRNAs by Northern hybridization. The mRNA levels for PAI-1 were elevated rapidly by TGFβ in both cell lines. This induction occurred in the presence of cycloheximide and thus was not dependent on protein synthesis. In fact, the effects of TGFβ and cycloheximide on PAI-1 mRNA were additive. In contrast, the induction of fibronectin, β-actin, and type I procollagen (synthesized only in WI-38 cells) was abrogated by cycloheximide. In general, the effects of TGFβ on the steady-state levels of mRNAs for fibronectin, actin, and type I procollagen mRNA were similar in the two cell types. However, the production of PAI-1 mRNA in response to TGFβ differed in the two cell types, being transient (peak within 5 h) in the carcinoma cells and more persistent in fibroblasts. Thus, the major difference in TGFβ regulation of PAI-1 mRNA between lung fibroblasts and carcinoma cells was the duration of the effect. These results, together with previous data, suggest that PAI-1 and plasminogen activators may be regulated oppositely by TGFβ. We therefore propose a model for TGFβ in the regulation of extracellular proteolytic activity.

AB - Transforming growth factor-β (TGFβ) is a growth modulator which stimulates the growth of fibroblasts but acts as a strong growth inhibitor for cells of epithelial origin. TGFβ also influences the production of extracellular matrix proteins and of proteases and protease inhibitors by cultured cells. One important protease inhibitor whose production is affected rapidly by TGFβ is the type-1 plasminogen activator inhibitor (PAI-1). To investigate the relationships between PAI-1 and the extracellular matrix, we analyzed the regulation by TGFβ of PAI-1, fibronectin, and type I procollagen in malignant human lung carcinoma cells (A549) and in human lung fibroblasts (WI-38). The expression of the respective genes was examined by polypeptide analyses and by measurements of the steady-state levels of the corresponding mRNAs by Northern hybridization. The mRNA levels for PAI-1 were elevated rapidly by TGFβ in both cell lines. This induction occurred in the presence of cycloheximide and thus was not dependent on protein synthesis. In fact, the effects of TGFβ and cycloheximide on PAI-1 mRNA were additive. In contrast, the induction of fibronectin, β-actin, and type I procollagen (synthesized only in WI-38 cells) was abrogated by cycloheximide. In general, the effects of TGFβ on the steady-state levels of mRNAs for fibronectin, actin, and type I procollagen mRNA were similar in the two cell types. However, the production of PAI-1 mRNA in response to TGFβ differed in the two cell types, being transient (peak within 5 h) in the carcinoma cells and more persistent in fibroblasts. Thus, the major difference in TGFβ regulation of PAI-1 mRNA between lung fibroblasts and carcinoma cells was the duration of the effect. These results, together with previous data, suggest that PAI-1 and plasminogen activators may be regulated oppositely by TGFβ. We therefore propose a model for TGFβ in the regulation of extracellular proteolytic activity.

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M3 - Article

VL - 263

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JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

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