Increase of circulating IGFBP-4 following genotoxic stress and its implication for senescence
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...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2020-03-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/54523 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832545074994479104 |
|---|---|
| author | Nicola Alessio Tiziana Squillaro Giovanni Di Bernardo Giovanni Galano Roberto De Rosa Mariarosa AB Melone Gianfranco Peluso Umberto Galderisi |
| author_facet | Nicola Alessio Tiziana Squillaro Giovanni Di Bernardo Giovanni Galano Roberto De Rosa Mariarosa AB Melone Gianfranco Peluso Umberto Galderisi |
| author_sort | Nicola Alessio |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0f0ec7a3b64049689e516595259736f5 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2020-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-0f0ec7a3b64049689e516595259736f52025-02-03T08:26:07ZengeLife Sciences Publications LtdeLife2050-084X2020-03-01910.7554/eLife.54523Increase of circulating IGFBP-4 following genotoxic stress and its implication for senescenceNicola Alessio0Tiziana Squillaro1Giovanni Di Bernardo2Giovanni Galano3Roberto De Rosa4Mariarosa AB Melone5Gianfranco Peluso6Umberto Galderisi7https://orcid.org/0000-0003-0909-7403Department of Experimental Medicine, Biotechnology and Molecular Biology Section, University of Campania “Luigi Vanvitelli,”, Naples, ItalyDepartment of Experimental Medicine, Biotechnology and Molecular Biology Section, University of Campania “Luigi Vanvitelli,”, Naples, ItalyASL Napoli 1 Centro P.S.I. Napoli Est - Barra, Naples, ItalyASL Napoli 1 Centro P.S.I. Napoli Est - Barra, Naples, ItalyASL Napoli 1 Centro P.S.I. Napoli Est - Barra, Naples, ItalyDepartment 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, ItalyResearch Institute of Terrestrial Ecosystems (IRET), CNR, Naples, ItalyDepartment 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 StatesSenescent 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.https://elifesciences.org/articles/54523mesenchymal stromal cellsparacrine signalingsenescenceSASPsecretome |
| spellingShingle | Nicola Alessio Tiziana Squillaro Giovanni Di Bernardo Giovanni Galano Roberto De Rosa Mariarosa AB Melone Gianfranco Peluso Umberto Galderisi Increase of circulating IGFBP-4 following genotoxic stress and its implication for senescence eLife mesenchymal stromal cells paracrine signaling senescence SASP secretome |
| title | Increase of circulating IGFBP-4 following genotoxic stress and its implication for senescence |
| title_full | Increase of circulating IGFBP-4 following genotoxic stress and its implication for senescence |
| title_fullStr | Increase of circulating IGFBP-4 following genotoxic stress and its implication for senescence |
| title_full_unstemmed | Increase of circulating IGFBP-4 following genotoxic stress and its implication for senescence |
| title_short | Increase of circulating IGFBP-4 following genotoxic stress and its implication for senescence |
| title_sort | increase of circulating igfbp 4 following genotoxic stress and its implication for senescence |
| topic | mesenchymal stromal cells paracrine signaling senescence SASP secretome |
| url | https://elifesciences.org/articles/54523 |
| work_keys_str_mv | AT nicolaalessio increaseofcirculatingigfbp4followinggenotoxicstressanditsimplicationforsenescence AT tizianasquillaro increaseofcirculatingigfbp4followinggenotoxicstressanditsimplicationforsenescence AT giovannidibernardo increaseofcirculatingigfbp4followinggenotoxicstressanditsimplicationforsenescence AT giovannigalano increaseofcirculatingigfbp4followinggenotoxicstressanditsimplicationforsenescence AT robertoderosa increaseofcirculatingigfbp4followinggenotoxicstressanditsimplicationforsenescence AT mariarosaabmelone increaseofcirculatingigfbp4followinggenotoxicstressanditsimplicationforsenescence AT gianfrancopeluso increaseofcirculatingigfbp4followinggenotoxicstressanditsimplicationforsenescence AT umbertogalderisi increaseofcirculatingigfbp4followinggenotoxicstressanditsimplicationforsenescence |