Subcytotoxic H2O2 Stress Triggers a Release of Transforming Growth Factor-β1, Which Induces Biomarkers of Cellular Senescence of Human Diploid Fibroblasts

Christophe Frippiat, Qin M. Chen, Stephanie Zdanov, Joao Padro Magalhaes, Jose Remacle, Olivier Toussaint

Research output: Contribution to journalArticle

245 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2531-2537
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number4
DOIs
StatePublished - Jan 26 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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