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mTOR signaling pathway regulation HIF-1 α effects on LPS induced intestinal mucosal epithelial model damage
- Source :
- BMC Molecular and Cell Biology, Vol 25, Iss 1, Pp 1-12 (2024)
- Publication Year :
- 2024
- Publisher :
- BMC, 2024.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 26618850
- Volume :
- 25
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- BMC Molecular and Cell Biology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.435c0bda656245b9b8584dd3ed2b7326
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s12860-024-00509-5