Journal of Biological Chemistry
Volume 276, Issue 4, 26 January 2001, Pages 2531-2537
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MECHANISMS OF SIGNAL TRANSDUCTION
Subcytotoxic H2O2 Stress Triggers a Release of Transforming Growth Factor-β1, Which Induces Biomarkers of Cellular Senescence of Human Diploid Fibroblasts*

https://doi.org/10.1074/jbc.M006809200Get rights and content
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Stress-induced premature senescence (SIPS) is induced 3 days after exposure of human diploid fibroblasts to subcytotoxic oxidative stress with H2O2, with appearance of several biomarkers of replicative senescence. In this work, we show that transforming growth factor-β1 (TGF-β1) regulates the induction of several of these biomarkers in SIPS: cellular morphology, senescence-associated β-galactosidase activity, increase in the steady-state level of fibronectin, apolipoprotein J, osteonectin, and SM22 mRNA. Indeed, the neutralization of TGF-β1 or its receptor (TGF-β RII) using specific antibodies decreases sharply the percentage of cells positive for the senescent-associated β-galactosidase activity and displaying a senescent morphology. In the presence of each of these antibodies, the steady-state level of fibronectin, osteonectin, apolipoprotein J, and SM22 mRNA is no more increased at 72 h after stress. Results obtained on fibroblasts retrovirally transfected with the human papillomavirus E7 cDNA suggest that retinoblastoma protein (Rb) regulates the expression of TGF-β1 in stressful conditions, leading to SIPS and overexpression of these four genes.

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Published, JBC Papers in Press, November 1, 2000, DOI 10.1074/jbc.M006809200

*

This work was supported in part by the European Union Biomed and Health Research Program “Genage” (BMH4-CT98-3149) and Fifth Framework Program “Protage” (QLK6-CT-1999-02193).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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Recipient of a fellowship from the Fonds pour la Recherche dans L'Industrie et L'Agriculture, Belgium.