Forkhead box P1 transcriptionally activates IGF-1 to lighten ox-LDL-induced endothelial cellular senescence by inactivating NLRP3 inflammasome.

Autor: Deng S; Key Laboratory of Tropical Translational Medicine of Ministry of Education & Key Laboratory of Brain Science Research Transformation in Tropical Environment of Hainan Province, School of Basic Medicine and Life Sciences, Hainan Medical University, No. 3, Xueyuan Road, Longhua District, Haikou, 571199, Hainan Province, China., Lao M; Key Laboratory of Tropical Translational Medicine of Ministry of Education & Key Laboratory of Brain Science Research Transformation in Tropical Environment of Hainan Province, School of Basic Medicine and Life Sciences, Hainan Medical University, No. 3, Xueyuan Road, Longhua District, Haikou, 571199, Hainan Province, China., Zheng H; Key Laboratory of Tropical Translational Medicine of Ministry of Education & Key Laboratory of Brain Science Research Transformation in Tropical Environment of Hainan Province, School of Basic Medicine and Life Sciences, Hainan Medical University, No. 3, Xueyuan Road, Longhua District, Haikou, 571199, Hainan Province, China., Hao J; Key Laboratory of Tropical Translational Medicine of Ministry of Education & Key Laboratory of Brain Science Research Transformation in Tropical Environment of Hainan Province, School of Basic Medicine and Life Sciences, Hainan Medical University, No. 3, Xueyuan Road, Longhua District, Haikou, 571199, Hainan Province, China. 18874774517@163.com.
Jazyk: angličtina
Zdroj: Biogerontology [Biogerontology] 2024 Nov 25; Vol. 26 (1), pp. 15. Date of Electronic Publication: 2024 Nov 25.
DOI: 10.1007/s10522-024-10151-5
Abstrakt: Endothelial cell (EC) senescence is a major contributor in atherosclerosis (AS) development. Herein, the role of forkhead box P transcription factor 1 (FOXP1) and insulin-like growth factor (IGF)-1 in regulating EC senescence during AS progression was investigated. The mRNA and protein expressions were assessed using qRT-PCR and western blot. IL-1β and IL-18 secretion levels were analyzed by ELISA. Cell viability and pyroptosis were determined by MTT assay and flow cytometry, respectively. SA β-Gal staining was used to measure cell senescence. Tube formation assay was adopted to detect the angiogenesis ability. Dual-luciferase reporter and ChIP assays were used to investigate the relationship between FOXP1 and IGF‑1. ox-LDL stimulation significantly reduced FOXP1 and IGF-1 expression levels in human aortic endothelial cells (HAECs). FOXP1 or IGF-1 overexpression both mitigated ox-LDL-induced cellular senescence and NLRP3 activation in HAECs. It was subsequently revealed that FOXB1 transcriptionally activated IGF-1 expression in HAECs by binding to IGF-1 promoter. Rescue experiments demonstrated that IGF-1 silencing abolished the inhibitory impact of FOXP1 overexpression on ox-LDL-induced cellular senescence and NLRP3 activation in HAECs. FOXP1 transcriptionally activated IGF-1 to lighten ox-LDL-induced endothelial cellular senescence by inactivating NLRP3 inflammasome.
Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable.
(© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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