Hyperbaric oxygen treatment increases intestinal stem cell proliferation through the mTORC1/S6K1 signaling pathway in Mus musculus

Biological Research

Research Article

Ignacio Casanova-Maldonado¹  Verónica Palma¹  Isaac Peña-Villalobos¹  David Arancibia¹  Pablo Lois² 

[1] 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;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;Education Department, Faculty of Humanities, Universidad Mayor, Santiago de Chile, Providencia, Chile;

关键词: Hyperbaric oxygen treatment;    Intestinal stem cells;    Progenitor cells;    Caloric restriction;    mTORC1;    S6K1;    Proliferation;    Clarity;    Rapamycin;   

DOI  :  10.1186/s40659-023-00444-3

 received in 2023-01-31, accepted in 2023-06-05,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundHyperbaric 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).ResultsWe 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.ConclusionsHBOT 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.

【 授权许可】

CC BY   
© The Author(s) 2023

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