eLife (Mar 2020)

Increase of circulating IGFBP-4 following genotoxic stress and its implication for senescence

  • Nicola Alessio,
  • Tiziana Squillaro,
  • Giovanni Di Bernardo,
  • Giovanni Galano,
  • Roberto De Rosa,
  • Mariarosa AB Melone,
  • Gianfranco Peluso,
  • Umberto Galderisi

DOI
https://doi.org/10.7554/eLife.54523
Journal volume & issue
Vol. 9

Abstract

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Senescent cells secrete several molecules, collectively named senescence-associated secretory phenotype (SASP). In the SASP of cells that became senescent following several in vitro chemical and physical stress, we identified the IGFBP-4 protein that can be considered a general stress mediator. This factor appeared to play a key role in senescence-paracrine signaling. We provided evidences showing that genotoxic injury, such as low dose irradiation, may promote an IGFBP-4 release in bloodstream both in mice irradiated with 100 mGy X-ray and in human subjects that received Computer Tomography. Increased level of circulating IGFBP-4 may be responsible of pro-aging effect. We found a significant increase of senescent cells in the lungs, heart, and kidneys of mice that were intraperitoneally injected with IGFBP-4 twice a week for two months. We then analyzed how genotoxic stressors may promote the release of IGFBP-4 and the molecular pathways associated with the induction of senescence by this protein.

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