circRNA-PTPN4 mediated regulation of FOXO3 and ZO-1 expression: implications for blood-brain barrier integrity and cognitive function in uremic encephalopathy.
Cell Biol Toxicol
; 40(1): 22, 2024 Apr 17.
Article
em En
| MEDLINE
| ID: mdl-38630149
ABSTRACT
Uremic encephalopathy (UE) poses a significant challenge in neurology, leading to the need to investigate the involvement of non-coding RNA (ncRNA) in its development. This study employed ncRNA-seq and RNA-seq approaches to identify fundamental ncRNAs, specifically circRNA and miRNA, in the pathogenesis of UE using a mouse model. In vitro and in vivo experiments were conducted to explore the circRNA-PTPN4/miR-301a-3p/FOXO3 axis and its effects on blood-brain barrier (BBB) function and cognitive abilities. The research revealed that circRNA-PTPN4 binds to and inhibits miR-301a-3p, leading to an increase in FOXO3 expression. This upregulation results in alterations in the transcriptional regulation of ZO-1, affecting the permeability of human brain microvascular endothelial cells (HBMECs). The axis also influences the growth, proliferation, and migration of HBMECs. Mice with UE exhibited cognitive deficits, which were reversed by overexpression of circRNA-PTPN4, whereas silencing FOXO3 exacerbated these deficits. Furthermore, the uremic mice showed neuronal loss, inflammation, and dysfunction in the BBB, with the expression of circRNA-PTPN4 demonstrating therapeutic effects. In conclusion, circRNA-PTPN4 plays a role in promoting FOXO3 expression by sequestering miR-301a-3p, ultimately leading to the upregulation of ZO-1 expression and restoration of BBB function in mice with UE. This process contributes to the restoration of cognitive abilities.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Barreira Hematoencefálica
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Cognição
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MicroRNAs
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Proteína Forkhead Box O3
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RNA Circular
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article