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Senescence-Associated Alterations in Matrisome of Mesenchymal Stem Cells Full article

Journal International Journal of Molecular Sciences
ISSN: 1422-0067 , E-ISSN: 1661-6596
Output data Year: 2024, Volume: 25, Number: 10, Article number : 5332, Pages count : DOI: 10.3390/ijms25105332
Tags mesenchymal stem cells (MSCs); senescence; extracellular matrix (ECM); matrisome; senescence-associated secretory phenotype (SASP)
Authors Matveeva Diana 1 , Kashirina Daria 1 , Ezdakova Mariia 1 , Larina Irina 1 , Buravkova Ludmila 1 , Ratushnyy Andrey 1
Affiliations
1 Institute of Biomedical Problems, Russian Academy of Sciences, Khoroshevskoye Shosse, 76a, 123007 Moscow, Russia

Abstract: The process of aging is intimately linked to alterations at the tissue and cellular levels. Currently, the role of senescent cells in the tissue microenvironment is still being investigated. Despite common characteristics, different cell populations undergo distinctive morphofunctional changes during senescence. Mesenchymal stem cells (MSCs) play a pivotal role in maintaining tissue homeostasis. A multitude of studies have examined alterations in the cytokine profile that determine their regulatory function. The extracellular matrix (ECM) of MSCs is a less studied aspect of their biology. It has been shown to modulate the activity of neighboring cells. Therefore, investigating age-related changes in the MSC matrisome is crucial for understanding the mechanisms of tissue niche ageing. This study conducted a broad proteomic analysis of the matrisome of separated fractions of senescent MSCs, including the ECM, conditioned medium (CM), and cell lysate. This is the first time such an analysis has been conducted. It has been established that there is a shift in production towards regulatory molecules and a significant downregulation of the main structural and adhesion proteins of the ECM, particularly collagens, fibulins, and fibrilins. Additionally, a decrease in the levels of cathepsins, galectins, S100 proteins, and other proteins with cytoprotective, anti-inflammatory, and antifibrotic properties has been observed. However, the level of inflammatory proteins and regulators of profibrotic pathways increases. Additionally, there is an upregulation of proteins that can directly cause prosenescent effects on microenvironmental cells (SERPINE1, THBS1, and GDF15). These changes confirm that senescent MSCs can have a negative impact on other cells in the tissue niche, not only through cytokine signals but also through the remodeled ECM.
Cite: Matveeva D. , Kashirina D. , Ezdakova M. , Larina I. , Buravkova L. , Ratushnyy A.
Senescence-Associated Alterations in Matrisome of Mesenchymal Stem Cells
International Journal of Molecular Sciences. 2024. V.25. N10. 5332 . DOI: 10.3390/ijms25105332 WOS Scopus РИНЦ PMID PMCID OpenAlex
Dates:
Submitted: Apr 3, 2024
Accepted: Apr 30, 2024
Published online: May 14, 2024
Identifiers:
Web of science: WOS:001234327100001
Scopus: 2-s2.0-85194218474
Elibrary: 67515367
PMID: 38791371
PMCID: PMC11120844
OpenAlex: W4396904906
Citing:
DB Citing
OpenAlex 5
Scopus 1
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