PMID- 37438828 OWN - NLM STAT- MEDLINE DCOM- 20230717 LR - 20230718 IS - 0717-6287 (Electronic) IS - 0716-9760 (Print) IS - 0716-9760 (Linking) VI - 56 IP - 1 DP - 2023 Jul 13 TI - Hyperbaric oxygen treatment increases intestinal stem cell proliferation through the mTORC1/S6K1 signaling pathway in Mus musculus. PG - 41 LID - 10.1186/s40659-023-00444-3 [doi] LID - 41 AB - 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: 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: 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. CI - (c) 2023. The Author(s). FAU - Casanova-Maldonado, Ignacio AU - Casanova-Maldonado I AUID- ORCID: 0000-0001-9502-570X AD - Laboratory of Stem Cells and Developmental Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Milenio Building Floor 3, 7800024, Santiago de Chile, Nunoa, Chile. Ignacio.casanova.m@gmail.com. FAU - Arancibia, David AU - Arancibia D AD - Laboratory of Stem Cells and Developmental Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Milenio Building Floor 3, 7800024, Santiago de Chile, Nunoa, Chile. FAU - Lois, Pablo AU - Lois P AD - Laboratory of Stem Cells and Developmental Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Milenio Building Floor 3, 7800024, Santiago de Chile, Nunoa, Chile. AD - Education Department, Faculty of Humanities, Universidad Mayor, Santiago de Chile, Providencia, Chile. FAU - Pena-Villalobos, Isaac AU - Pena-Villalobos I AD - Laboratory of Stem Cells and Developmental Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Milenio Building Floor 3, 7800024, Santiago de Chile, Nunoa, Chile. isaac.pena@uchile.cl. FAU - Palma, Veronica AU - Palma V AD - Laboratory of Stem Cells and Developmental Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Milenio Building Floor 3, 7800024, Santiago de Chile, Nunoa, Chile. vpalma@uchile.cl. LA - eng GR - D09E1047/FONDEF/ GR - 3180108/FONDECYT/ GR - 1140697/FONDECYT/ GR - 1110237/FONDECYT/ PT - Journal Article DEP - 20230713 PL - England TA - Biol Res JT - Biological research JID - 9308271 RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) RN - S88TT14065 (Oxygen) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Animals MH - Mice MH - Cell Proliferation MH - *Hyperbaric Oxygenation MH - Intestines/cytology MH - Mechanistic Target of Rapamycin Complex 1 MH - Oxygen MH - *Signal Transduction MH - Sirolimus/pharmacology MH - *Stem Cells/drug effects PMC - PMC10339527 OTO - NOTNLM OT - Caloric restriction OT - Clarity OT - Hyperbaric oxygen treatment OT - Intestinal stem cells OT - Progenitor cells OT - Proliferation OT - Rapamycin OT - S6K1 OT - mTORC1 COIS- The authors declare no competing financial interests. EDAT- 2023/07/13 01:06 MHDA- 2023/07/14 13:08 PMCR- 2023/07/13 CRDT- 2023/07/12 23:51 PHST- 2023/01/31 00:00 [received] PHST- 2023/06/05 00:00 [accepted] PHST- 2023/07/14 13:08 [medline] PHST- 2023/07/13 01:06 [pubmed] PHST- 2023/07/12 23:51 [entrez] PHST- 2023/07/13 00:00 [pmc-release] AID - 10.1186/s40659-023-00444-3 [pii] AID - 444 [pii] AID - 10.1186/s40659-023-00444-3 [doi] PST - epublish SO - Biol Res. 2023 Jul 13;56(1):41. doi: 10.1186/s40659-023-00444-3.