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Research Article Free access | 10.1172/JCI119365

TGFbeta1 regulates gene expression of its own converting enzyme furin.

F Blanchette, R Day, W Dong, M H Laprise, and C M Dubois

Department of Pediatrics, Faculty of Medicine, University of Sherbrooke, Québec, Canada.

Find articles by Blanchette, F. in: JCI | PubMed | Google Scholar

Department of Pediatrics, Faculty of Medicine, University of Sherbrooke, Québec, Canada.

Find articles by Day, R. in: JCI | PubMed | Google Scholar

Department of Pediatrics, Faculty of Medicine, University of Sherbrooke, Québec, Canada.

Find articles by Dong, W. in: JCI | PubMed | Google Scholar

Department of Pediatrics, Faculty of Medicine, University of Sherbrooke, Québec, Canada.

Find articles by Laprise, M. in: JCI | PubMed | Google Scholar

Department of Pediatrics, Faculty of Medicine, University of Sherbrooke, Québec, Canada.

Find articles by Dubois, C. in: JCI | PubMed | Google Scholar

Published April 15, 1997 - More info

Published in Volume 99, Issue 8 on April 15, 1997
J Clin Invest. 1997;99(8):1974–1983. https://doi.org/10.1172/JCI119365.
© 1997 The American Society for Clinical Investigation
Published April 15, 1997 - Version history
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Abstract

TGFbeta1 is known for its potent and diverse biological effects, including immune regulation, and cell growth and differentiation. We have recently shown that TGFbeta1 precursor is processed by human furin COOH-terminal to the R-H-R-R278 cleavage site to generate authentic mature TGFbeta1. In the present study, we demonstrate that steady-state furin mRNA levels are increased in rat synovial cells by 2 and 20 ng/ml TGFbeta1. Stimulation with TGFbeta1 results in a significant increase in furin mRNA levels, starting at 3 h with the peak effect observed at 12 h (2.5-fold increase +/-0.4). TGFbeta1 did not increase furin mRNA stability, and treatment of synovial cells with actinomycin D, before TGFbeta1 addition prevented the increase in fur gene expression, suggesting that the observed regulation occurs at the level of gene transcription. Treatment of synovial and NRK-49F fibroblastic cells with exogenous TGFbeta1 (5 ng/ml) or TGFbeta2 (10 ng/ml) translates into an increase in pro-TGFbeta1 processing as evidenced by the appearance of a 40-kD immunoreactive band corresponding to the TGFbeta1 NH2-terminal pro-region. Furin processing activity stimulated by TGFbeta2 correlates with significant increase in extracellular mature and heat-activable TGFbeta1 as determined by an isoform-specific ELISA assay. Taken together, these results demonstrate for the first time that TGFbeta1 upregulates gene expression of its own converting enzyme, and that this expression is translated into augmented processing of the TGFbeta1 precursor form. Such adaptive responsiveness of the TGFbeta1 convertase may represent an important aspect of TGFbeta1 bioavailibility in TGFbeta1-related processes and pathological conditions.

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