Repeated Exposure to Hyperbaric Hyperoxia Affects Mitochondrial Functions of the Lung Fibroblasts

Dejmek, J; Kohoutová, M; Kripnerová, Michaela; Čedíková, Miroslava; Tůma, Zdeněk; Babuška, Václav; Bolek, Lukáš; Kuncová, Jitka

doi:10.33549/physiolres.934046

Cited by 9 publications

(3 citation statements)

References 50 publications

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“…These results were in concordance with previous reports of mitochondrial oxygen consumption [ 37 , 67 ] and our previous work, where we showed that HBOT for ten consecutive days did not change the basal metabolic rates in mice [ 49 ]. They are also consistent with a recent in vitro analysis of lung fibroblast treated with HBOT, reporting no changes in CS activity [ 20 ]. Notwithstanding, it is remarkable how a treatment that increases oxygen tension does not alter oxidative metabolism in the intestinal epithelium, while other reports indicate that acute HBOT does generate changes in tissues like the brain or skeletal muscle [ 34 , 45 ], indicating that the response to HBOT is tissue dependent.…”

Section: Discussionsupporting

confidence: 92%

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

et al. 2023

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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.

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Section: Discussionsupporting

confidence: 92%

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

et al. 2023

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“…These results were in concordance with our previous work, where we showed that using HBOT for 10 consecutive days did not change the basal metabolic rates of mice 2018). They are also in line with a recent in vitro analysis of lung fibroblast where no changes in CS activity were reported (Dejmek et al;2018).…”

Section: Discussionsupporting

confidence: 89%

Hyperbaric oxygen treatment increases intestinal stem cell proliferation through mTORc1 signaling in Mus musculus

casanova¹,

Peña-Villalobos²,

Arancibia-Altamirano³

et al. 2020

Preprint

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Background: Hyperbaric oxygen treatment (HBOT) has been used for more than a decade to treat diverse diseases like diabetic foot ulcers and ischemic injuries. More recently, HBOT has been reported to modulate proliferation of neural and intestinal stem cell populations, but the molecular mechanisms underlying these effects are not completely understood. Objective: In this study we aimed to determine HBOT stem cell modulation by evaluating in particular the role of the mTOR complex 1 (mTORc1), a key regulator of cell metabolism that modifies its activity depending on oxygen levels, as a potential mediator of HBOT in murine intestinal stem cells (ISCs). Methods: Mouse were exposed to 10 or 20 HBOT sessions and the proliferation of the ISCs were analyzed by immunofluorescence or immunohistochemistry using the specific ISCs marker, Olfm4. The regulation of HBOT and mTORc1 pathway was analyzed through S6K1 phosphorylation by western-blot and through the inhibition by rapamycin. Results: We discovered that acute HBOT can increase proliferation of ISCs in a synchronous fashion without affecting the animal’s oxidative metabolism. Noteworthy, the mTORc1 inhibitor rapamycin also increases the proliferation of ISCs. This effect has been attributed to its capacity to mimic a caloric restriction (CR). Interestingly, the combination of HBOT and rapamycin does not have a synergic effect. Nevertheless, HBOT can recover rapamycin induced mTORc1 inhibition, possibly acting through a competitive modulation on mTORC1. Conclusions: Collectively, our results suggest that HBOT proliferative effect on ISCs is modulated by mTORc1 signaling representing a promising new approach to treat intestinal conditions.

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“…Conversely, the impact of hyperoxia on the adult lung appears to be relatively mild with current HBO therapies being reported to be clinically safe [7]. Previous studies suggest that HBO exposure induces oxidative stress, which activates antioxidant systems [8][9][10][11]. In addition, several conditions may benefit from the potentially protective effects of HBO exposure, including toxic-induced lung injury [12][13][14][15], smoke-induced pulmonary edema [16], hyperoxic acute lung injury [17], and acute pancreatitis-induced lung injury [18].…”

Section: Introductionmentioning

confidence: 99%

Deconvolution of RNA-Seq Analysis of Hyperbaric Oxygen-Treated Mice Lungs Reveals Mesenchymal Cell Subtype Changes

Yuan

Zhou

et al. 2020

IJMS

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Hyperbaric oxygen (HBO) is widely applied to treat several hypoxia-related diseases. Previous studies have focused on the immediate effect of HBO-exposure induced oxidative stress on the lungs, but knowledge regarding the chronic effects from repetitive HBO exposure is limited, especially at the gene expression level. We found that repetitive HBO exposure did not alter the morphology of murine lungs. However, by deconvolution of RNA-seq from those mice lungs using CIBERSORTx and the expression profile matrices of 8 mesenchymal cell subtypes obtained from bleomycin-treated mouse lungs, we identify several mesenchymal cell subtype changes. These include increases in Col13a1 matrix fibroblasts, mesenchymal progenitors and mesothelial cell populations and decreases in lipofibroblasts, endothelial and Pdgfrb high cell populations. Our data suggest that repetitive HBO exposure may affect biological processes in the lungs such as response to wounding, extracellular matrix, vasculature development and immune response.

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Repeated Exposure to Hyperbaric Hyperoxia Affects Mitochondrial Functions of the Lung Fibroblasts

Cited by 9 publications

References 50 publications

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

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

Hyperbaric oxygen treatment increases intestinal stem cell proliferation through mTORc1 signaling in Mus musculus

Deconvolution of RNA-Seq Analysis of Hyperbaric Oxygen-Treated Mice Lungs Reveals Mesenchymal Cell Subtype Changes

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