Research Paper Volume 8, Issue 7 pp 1316—1327
Unbiased analysis of senescence associated secretory phenotype (SASP) to identify common components following different genotoxic stresses
- 1 Genome and Stem Cell Center (GENKOK), Erciyes University, Kayseri, Turkey
- 2 Department of Biology, Faculty of Sciences, Erciyes University, Kayseri, Turkey
- 3 Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, PA 19122, USA
- 4 Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Naples, Italy
- 5 Institute of Bioscience and Bioresources, CNR, Naples, Italy
Received: March 16, 2016 Accepted: May 28, 2016 Published: June 9, 2016
https://doi.org/10.18632/aging.100971How to Cite
Abstract
Senescent cells secrete senescence-associated secretory phenotype (SASP) proteins to carry out several functions, such as sensitizing surrounding cells to senesce; immunomodulation; impairing or fostering cancer growth; and promoting tissue development. Identifying secreted factors that achieve such tasks is a challenging issue since the profile of secreted proteins depends on genotoxic stress and cell type. Currently, researchers are trying to identify common markers for SASP. The present investigation compared the secretome composition of five different senescent phenotypes in two different cell types: bone marrow and adipose mesenchymal stromal cells (MSC). We induced MSC senescence by oxidative stress, doxorubicin treatment, X-ray irradiation, and replicative exhaustion. We took advantage of LC-MS/MS proteome identification and subsequent gene ontology (GO) evaluation to perform an unbiased analysis (hypothesis free manner) of senescent secretomes. GO analysis allowed us to distribute SASP components into four classes: extracellular matrix/cytoskeleton/cell junctions; metabolic processes; ox-redox factors; and regulators of gene expression.
We used Ingenuity Pathway Analysis (IPA) to determine common pathways among the different senescent phenotypes. This investigation, along with identification of eleven proteins that were exclusively expressed in all the analyzed senescent phenotypes, permitted the identification of three key signaling paths: MMP2 - TIMP2; IGFBP3 - PAI-1; and Peroxiredoxin 6 - ERP46 - PARK7 - Cathepsin D - Major vault protein. We suggest that these paths could be involved in the paracrine circuit that induces senescence in neighboring cells and may confer apoptosis resistance to senescent cells.