Paracrine senescence of human endometrial mesenchymal stem cells: a role for the insulin-like growth factor binding protein 3.
| Title: | Paracrine senescence of human endometrial mesenchymal stem cells: a role for the insulin-like growth factor binding protein 3. |
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| Authors: | Vassilieva I; Department of Intracellular Signaling and Transport, Institute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, Russia.; Kosheverova V; Department of Intracellular Signaling and Transport, Institute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, Russia.; Vitte M; Department of Intracellular Signaling and Transport, Institute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, Russia.; Kamentseva R; Department of Intracellular Signaling and Transport, Institute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, Russia.; Shatrova A; Department of Intracellular Signaling and Transport, Institute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, Russia.; Tsupkina N; Department of Intracellular Signaling and Transport, Institute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, Russia.; Skvortsova E; Department of Intracellular Signaling and Transport, Institute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, Russia.; Borodkina A; Department of Intracellular Signaling and Transport, Institute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, Russia.; Tolkunova E; Department of Intracellular Signaling and Transport, Institute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, Russia.; Nikolsky N; Department of Intracellular Signaling and Transport, Institute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, Russia.; Burova E; Department of Intracellular Signaling and Transport, Institute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, Russia. |
| Source: | Aging [Aging (Albany NY)] 2020 Jan 17; Vol. 12 (2), pp. 1987-2004. Date of Electronic Publication: 2020 Jan 17. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Impact Journals, LLC Country of Publication: United States NLM ID: 101508617 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1945-4589 (Electronic) Linking ISSN: 19454589 NLM ISO Abbreviation: Aging (Albany NY) Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Albany, NY : Impact Journals, LLC |
| MeSH Terms: | Paracrine Communication*; Endometrium/*cytology ; Endometrium/*metabolism ; Mesenchymal Stem Cells/*metabolism; Hydrogen Peroxide/metabolism ; Hydrogen Peroxide/pharmacology ; Insulin-Like Growth Factor Binding Protein 3/genetics ; Insulin-Like Growth Factor Binding Protein 3/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Cellular Senescence ; Endocytosis ; Female ; Humans ; MAP Kinase Signaling System ; Phosphatidylinositol 3-Kinases ; Protein Transport ; Signal Transduction |
| Abstract: | Stress-induced premature cell senescence is well recognized to be accompanied by emerging the senescence-associated secretory phenotype (SASP). Secreted SASP factors can promote the senescence of normal neighboring cells through autocrine/paracrine pathways and regulate the senescence response, as well. Regarding human endometrium-derived mesenchymal stem cells (MESCs), the SASP regulation mechanisms as well as paracrine activity of senescent cells have not been studied yet. Here, we examined the role of insulin-like growth factor binding protein 3 (IGFBP3) in the paracrine senescence induction in young MESCs. The H2O2-induced premature senescence of MESCs led to increased IGFBP3 in conditioned media (CM). The inhibitory analysis of both MAPK and PI3K signaling pathways showed that IGFBP3 releasing from senescent cells is mainly regulated by PI3K/Akt pathway activity. IGFBP3 appears to be an important senescence-mediating factor as its immunodepletion from the senescent CM weakened the pro-senescent effect of CM on young MESCs and promoted their growth. In contrast, young MESCs acquired the senescence phenotype in response to simultaneous addition of recombinant IGFBP3 (rIGFBP3). The mechanism of extracellular IGFBP3 internalization was also revealed. The present study is the first to demonstrate a significant role of extracellular IGFBP3 in paracrine senescence induction of young MESCs. |
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| Contributed Indexing: | Keywords: IGFBP3; endocytosis; endometrial stem cells; paracrine senescence; secretome |
| Substance Nomenclature: | BBX060AN9V (Hydrogen Peroxide); 0 (Insulin-Like Growth Factor Binding Protein 3); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) |
| Entry Date(s): | Date Created: 20200118 Date Completed: 20210108 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC7053595 |
| DOI: | 10.18632/aging.102737 |
| PMID: | 31951594 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't