Hyperbaric oxygen treatment increases intestinal stem cell proliferation through the mTORC1/S6K1 signaling pathway in Mus musculus.
Caloric restriction
Clarity
Hyperbaric oxygen treatment
Intestinal stem cells
Progenitor cells
Proliferation
Rapamycin
S6K1
mTORC1
Journal
Biological research
ISSN: 0717-6287
Titre abrégé: Biol Res
Pays: England
ID NLM: 9308271
Informations de publication
Date de publication:
13 Jul 2023
13 Jul 2023
Historique:
received:
31
01
2023
accepted:
05
06
2023
medline:
14
7
2023
pubmed:
13
7
2023
entrez:
12
7
2023
Statut:
epublish
Résumé
Hyperbaric oxygen treatment (HBOT) has been reported to modulate the proliferation of neural and mesenchymal stem cell populations, but the molecular mechanisms underlying these effects are not completely understood. In this study, we aimed to assess HBOT somatic stem cell modulation by evaluating the role of the mTOR complex 1 (mTORC1), a key regulator of cell metabolism whose activity is modified depending on oxygen levels, as a potential mediator of HBOT in murine intestinal stem cells (ISCs). We discovered that acute HBOT synchronously increases the proliferation of ISCs without affecting the animal's oxidative metabolism through activation of the mTORC1/S6K1 axis. mTORC1 inhibition by rapamycin administration for 20 days also increases ISCs proliferation, generating a paradoxical response in mice intestines, and has been proposed to mimic a partial starvation state. Interestingly, the combination of HBOT and rapamycin does not have a synergic effect, possibly due to their differential impact on the mTORC1/S6K1 axis. HBOT can induce an increase in ISCs proliferation along with other cell populations within the crypt through mTORC1/S6K1 modulation without altering the oxidative metabolism of the animal's small intestine. These results shed light on the molecular mechanisms underlying HBOT therapeutic action, laying the groundwork for future studies.
Sections du résumé
BACKGROUND
BACKGROUND
Hyperbaric oxygen treatment (HBOT) has been reported to modulate the proliferation of neural and mesenchymal stem cell populations, but the molecular mechanisms underlying these effects are not completely understood. In this study, we aimed to assess HBOT somatic stem cell modulation by evaluating the role of the mTOR complex 1 (mTORC1), a key regulator of cell metabolism whose activity is modified depending on oxygen levels, as a potential mediator of HBOT in murine intestinal stem cells (ISCs).
RESULTS
RESULTS
We discovered that acute HBOT synchronously increases the proliferation of ISCs without affecting the animal's oxidative metabolism through activation of the mTORC1/S6K1 axis. mTORC1 inhibition by rapamycin administration for 20 days also increases ISCs proliferation, generating a paradoxical response in mice intestines, and has been proposed to mimic a partial starvation state. Interestingly, the combination of HBOT and rapamycin does not have a synergic effect, possibly due to their differential impact on the mTORC1/S6K1 axis.
CONCLUSIONS
CONCLUSIONS
HBOT can induce an increase in ISCs proliferation along with other cell populations within the crypt through mTORC1/S6K1 modulation without altering the oxidative metabolism of the animal's small intestine. These results shed light on the molecular mechanisms underlying HBOT therapeutic action, laying the groundwork for future studies.
Identifiants
pubmed: 37438828
doi: 10.1186/s40659-023-00444-3
pii: 10.1186/s40659-023-00444-3
pmc: PMC10339527
doi:
Substances chimiques
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
Oxygen
S88TT14065
Sirolimus
W36ZG6FT64
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
41Subventions
Organisme : FONDEF
ID : D09E1047
Organisme : FONDECYT
ID : 3180108
Organisme : FONDECYT
ID : 1140697
Organisme : FONDECYT
ID : 1110237
Informations de copyright
© 2023. The Author(s).
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