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

eLife

Giovanni Di Bernardo¹  Giovanni Galano¹  Roberto De Rosa¹  Nicola Alessio²  Tiziana Squillaro²  Umberto Galderisi³  Mariarosa AB Melone⁴  Gianfranco Peluso⁵ 

[1] ASL Napoli 1 Centro P.S.I. Napoli Est - Barra, Naples, Italy;Department of Experimental Medicine, Biotechnology and Molecular Biology Section, University of Campania “Luigi Vanvitelli,”, Naples, Italy;Department of Experimental Medicine, Biotechnology and Molecular Biology Section, University of Campania “Luigi Vanvitelli,”, Naples, Italy;Research Institute of Terrestrial Ecosystems (IRET), CNR, Naples, Italy;Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, United States;Department of Medical, Surgical, Neurological, Metabolic Sciences, and Aging, 2nd Division of Neurology, Center for Rare Diseases and InterUniversity Center for Research in Neurosciences, University of Campania 'Luigi Vanvitelli', Naples, Italy;Research Institute of Terrestrial Ecosystems (IRET), CNR, Naples, Italy;

关键词: mesenchymal stromal cells;    paracrine signaling;    senescence;    SASP;    secretome;    Human;    Mouse;   

DOI  :  10.7554/eLife.54523

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY