Dataset Information

Replicative and irradiation-induced senescence of endothelial cells

ABSTRACT: This research investigates cellular senescence in human umbilical vein endothelial cells (HUVECs), focusing on their implications for cardiovascular diseases. We employed RNA sequencing to analyze gene expression changes in HUVECs subjected to replicative- or stress-induced senescence via ionizing radiation. Our findings reveal that both senescence types exhibit significant upregulation of genes associated with epithelial-mesenchymal transition (EMT) and inflammatory pathways, indicating a shared molecular response. Experimental validation confirmed reduced proliferation and increased secretion of pro-inflammatory cytokines (IL-6 and IL-8) in senescent cells and substantiated the upregulation of EMT marker genes. Additionally, we observed impaired wound healing capacity in senescent cells, highlighting the functional consequences of these cellular state. Our study underscores the critical role of senescence-related changes, contributing to the understanding of age-related cardiovascular pathologies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE294733 | GEO | 2025/06/18

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:BACKGROUND: Periodontal ligament mesenchymal stem cells (PDLSCs) are a promising cell resource for cell-based regenerative medicine in dentistry. PDLSCs inevitably acquire a senescent phenotype after prolonged in vitro expansion, and the key regulators of cells during replicative senescence remain unclear.METHODS: We cultured periodontal ligament stem cells to passages 4, 10 and 20 (P4, P10, P20). The senescent phenotypes, proliferation and migration ability of PDLSCs (P4, P10, P20) were detected, and non-targeted metabonomic sequencing was performed. We treated PDLSCs with AICAR and detected the expression of FOXO1, FOXO3a, FOXO6 and AMPK phosphorylation (p-AMPK) levels of replicating senescent PDLSCs to explore the correlation between the metabolic changes and the AMPK pathway.RESULTS: Immunofluorescence staining of γ-H2AX, β-galactosidase staining, cell scratch test and qPCR were performed to confirm the occurrence of replicative senescence in PDLSCs during passaging. Three groups of cells at passage 4 (P4), passage 10 (P10) and passage 20 (P20) were collected for non-targeted metabolomics analysis. Metabonomic sequencing showed that the metabolism of replicative senescence in PDLSCs varied significantly. In particular, the content of fatty acid metabolites decreased with senescence, including capric acid, stearic acid, myristic acid and dodecanoic acid. KEGG pathway analysis showed that the AMPK signaling pathway was closely related to AMP levels. The AMP:ATP ratio increased in senescent PDLSCs; however, the levels of p-AMPK and the profile of FOXO1 and FOXO3a, which are downstream of the AMPK signaling pathway, decreased with senescence. We treated PDLSCs with AICAR, an activator of the AMPK pathway, and the phosphorylated AMPK level at P20 PDLSCs was partially restored. CONCLUSION: In summary, our study suggests that the metabolic process of PDLSCs is active in the early stage of senescence, prefers to consume fatty acids, and is attenuated in the later stages of senescence. AMP accumulates in replicative senescent PDLSCs; however, the sensitivity of AMPK phosphorylation sites is impaired, causing senescent PDLSCs to fail to respond to changes in energy metabolism. Our findings provide a new basis for the clinical application of periodontal ligament stem cells.

Dataset Information

Replicative and irradiation-induced senescence of endothelial cells

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets