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
in 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Lipopolysaccharides
/
Hypoxia-Inducible Factor 1, alpha Subunit
/
TOR Serine-Threonine Kinases
/
Intestinal Mucosa
Limits:
Humans
Language:
En
Journal:
BMC Mol Cell Biol
Year:
2024
Document type:
Article