mTOR signaling pathway regulation HIF-1 α effects on LPS induced intestinal mucosal epithelial model damage.
BMC Mol Cell Biol
; 25(1): 13, 2024 Apr 23.
Article
em En
| MEDLINE
| ID: mdl-38654163
ABSTRACT
BACKGROUND:
Sepsis-induced small-intestinal injury is associated with increased morbidity and mortality. Our previous study and other papers have shown that HIF-1α has a protective effect on intestinal mucosal injury in septic rats. The purpose of this study is to further verify the protective effect of HIF-1α on intestinal mucosa and its molecular mechanism in vitro experiments.METHODS:
Caco-2 cells were selected and experiment was divided into 2 parts. Part I HIF-1α activator and inhibitor were used to treat lipopolysacchrides (LPS)-stimulated Caco-2 cells respectively, to explore the effect of HIF-1α on LPS induced Caco-2 cell epithelial model; Part II mTOR activator or inhibitor combined with or without HIF-1α activator, inhibitor to treat LPS-stimulated Caco-2 cells respectively, and then the molecular mechanism of HIF-1α reducing LPS induced Caco-2 cell epithelial model damage was detected.RESULTS:
The results showed that HIF-1α activator decreased the permeability and up regulated tight junction (TJ) expression, while HIF-1α inhibitor had the opposite effect with the HIF-1α activator. mTOR activation increased, while mTOR inhibition decreased HIF-1α protein and expression of its downstream target molecules, which can be attenuated by HIF-1α activator or inhibitor.CONCLUSION:
This study once again confirmed that HIF-1α alleviates LPS-induced mucosal epithelial model damage through P70S6K signalling pathway. It is of great value to explore whether HIF-2α plays crucial roles in the regulation of mucosal epithelial model functions in the future.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Lipopolissacarídeos
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Subunidade alfa do Fator 1 Induzível por Hipóxia
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Serina-Treonina Quinases TOR
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Mucosa Intestinal
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article