MiR-29a mediates the apoptotic effects of TNF-α on endothelial cells through inhibiting PI3K/AKT/BCL-2 axis.
apoptosis
atherosclerosis (AS)
human umbilical vascular endothelial cells (HUVECs)
microRNA (miR)-29a
tumor necrosis factor (TNF)-α
Journal
Journal of biochemical and molecular toxicology
ISSN: 1099-0461
Titre abrégé: J Biochem Mol Toxicol
Pays: United States
ID NLM: 9717231
Informations de publication
Date de publication:
04 Dec 2023
04 Dec 2023
Historique:
revised:
04
09
2023
received:
06
12
2022
accepted:
20
11
2023
medline:
4
12
2023
pubmed:
4
12
2023
entrez:
4
12
2023
Statut:
aheadofprint
Résumé
Endothelial cell apoptosis driven by inflammation (TNF-α) plays a critical role in the pathogenesis of atherosclerosis, but the exact molecular mechanisms are not clearly elucidated. MicroRNA (miR)-29 families (a/b/c) take important roles in pathophysiological processes of atherosclerosis, also the underlying mechanisms have not been fully clarified. The aims are to explore whether or not miR-29 families mediate the apoptotic effects of TNF-α on endothelial cells and uncover the underlying molecular mechanisms. In this study, MTT assay and flow cytometer analysis were employed respectively to determine the proliferation and apoptosis of human umbilical vascular endothelial cells (HUVECs) under TNF-α exposure. Real-time quantitative PCR and western blot were performed to detect the levels of target RNAs and proteins/their phosphorylation in HUVECs. TNF-α could inhibit HUVEC proliferation and induce HUVEC apoptosis in a positive dose- and time-dependent manner, with a similar way of miR-29a upregulation, but no effects on miR-29b/c. Upregulation of miR-29a with its mimics enhanced the apoptotic effect of TNF-α on HUVECs, but downregulation of miR-29a using anti-miR-29a blocked up its apoptotic effect. MiR-29a inhibited the expression of PI3Kp85α and Bcl-2 and blocked up the signal transduction of PI3K/AKT/Bcl-2 axis to mediate the apoptotic effect of TNF-α on HUVECs. Mediating the inflammation-driven endothelial cell apoptosis is an important biology mechanism by which miR-29a promotes atherosclerosis and its complications. MiR-29a will be a potential diagnostic and therapeutic target for atherosclerotic cardiovascular diseases; it is worthwhile to further study.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23598Subventions
Organisme : Foundation of State Key Laboratory of Organic Geochemistry, GIGCAS
ID : SKLOG-202213
Organisme : National Natural Science Foundation of China
ID : 41877390
Informations de copyright
© 2023 Wiley Periodicals LLC.
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