The role of SASP in ischemic stroke: a deep dive into cellular mechanisms
BackgroundThe escalating incidence of ischemic stroke (IS) exerts a heavy toll on global health. Aging, a prominent risk factor, implicates the senescence-associated secretory phenotype (SASP) in IS pathogenesis. We postulated that alterations in SASP-related factor expression during IS correlate wi...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
|
| Series: | Frontiers in Neurology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2024.1513357/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | BackgroundThe escalating incidence of ischemic stroke (IS) exerts a heavy toll on global health. Aging, a prominent risk factor, implicates the senescence-associated secretory phenotype (SASP) in IS pathogenesis. We postulated that alterations in SASP-related factor expression during IS correlate with remodeling of intercellular interaction networks and disease advancement. The present study endeavored to preliminarily dissect the SASP-IS nexus via combined bulk and single-cell transcriptome analysis.MethodsAggregated expression profiles from human peripheral blood bulk chips and MCAO mouse single-cell sequencing data, followed by SASP gene analysis. Executed protein interaction network and enrichment assays. Investigated immune infiltration in stroke patients, managed quality control and annotation of single-cell data, cherry-picked central cells based on SASP scores, unearthed essential genes via enrichment analysis, conducted pseudo-time and intercellular communication studies, and prognosticated drugs for hub genes. Finally, authenticated core gene expression in serum of MCAO and Sham rats using real-time fluorescent polymerase chain reaction (RT-qPCR).ResultsFourteen hub genes were discerned. Seven cell types were annotated in MCAO mouse peripheral blood single-cell data. Basophils exhibited the highest SASP scores, with Lcp1 upregulated and Ccl3 downregulated in basophils of the MCAO group. Enrichment analysis divulged a significant association of Ccl3 with the cell apoptosis pathway and Lcp1 with immune responses. The Ccl3 gene is pivotal in basophils and basophil-neutrophil crosstalk. Additionally, we forecasted nagrestipen’s regulatory function on Ccl3. RT-qPCR demonstrated a marked elevation in Lcp1 mRNA and a pronounced reduction in Ccl3 in the MCAO group relative to the Sham group.ConclusionThe Ccl3 gene in basophils and its immune cell interaction is a linchpin in the IS immune microenvironment. Ccl3 and Lcp1 might potentially modulate IS progression by influencing SASP, proffering novel prospects for IS clinical diagnosis and treatment. |
|---|---|
| ISSN: | 1664-2295 |