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Cell Proliferation

Cell Proliferation

IF: 5.9
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SLC30A4‐AS1 Mediates the Senescence of Periodontal Ligament Stem Cells in Inflammatory Environments via?the Alternative Splicing of TP53BP1

Published:21 November 2024 DOI: 10.1111/cpr.13778 PMID: 39572253
Mei Xu, Dian Gan, Xi‐Yu Zhang, Xiao‐Tao He, Rui Xin Wu, Yuan Yin, Rui Jin, Lin Li, Yu‐Jie Tan, Fa‐Ming Chen, Xuan Li, Bei‐Min Tian

Abstract

Periodontal ligament stem cells (PDLSCs) are key cells that suppress periodontal damage during both the progression and recovery stages of periodontitis. Although substantial evidence has demonstrated that incubation under an inflammatory condition may accelerate senescence of PDLSCs, whether cellular senescence in response to inflammatory incubation contributes to cell dysfunction remain unexplored. In this study, we first observed inflammation-caused PDLSC senescence in periodontitis based on comparisons of matched patients, and this cellular senescence was demonstrated in healthy cells that were subjected to inflammatory conditions. We subsequently designed further experiments to investigate the possible mechanism underlying inflammation-induced PDLSC senescence with a particular focus on the role of long noncoding RNAs (lncRNAs). LncRNA microarray analysis and functional gain/loss studies revealed SLC30A4-AS1 as a regulator of inflammation-mediated PDLSC senescence. By full-length transcriptome sequencing, we found that SLC30A4-AS1 interacted with SRSF3 to affect the alternative splicing (AS) of TP53BP1 and alter the expression of TP53BP1-204. Further functional studies showed that decreased expression of TP53BP1-204 reversed PDLSC senescence, and SLC30A4-AS1 overexpression-induced PDLSC senescence was abolished by TP53BP1-204 knockdown. Our data suggest for the first time that SLC30A4-AS1 plays a key role in regulating PDLSC senescence in inflammatory environments by modulating the AS of TP53BP1.

Substances (2)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Bovine albumin 9048-46-8 N/A 495 suppliers $15.00-$17060.00
FETUIN 9014-81-7 NULL 66 suppliers $37.07-$4380.00

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