Oxidative stress induces club cell proliferation and pulmonary fibrosis in Atp8b1 mutant mice

Fukumoto, Jutaro; Leung, Joseph; Cox, Ruan; Czachor, Alexander; Parthasarathy, Prasanna Tamarapu; Lagishetty, Venu; Mandry, Maria; Hosseinian, Nima; Patel, Priyanshi; Perry, Brittany; Breitzig, Mason; Alleyn, Matthew; Failla, Athena; Cho, Young Ae; Cooke, Andrew J.; Galam, Lakshmi; Soundararajan, Ramani; Sharma, Nirmal S.; Lockey, Richard F.; Kolliputi, Narasaiah

doi:10.18632/aging.101742

Cited by 16 publications

(22 citation statements)

References 56 publications

(60 reference statements)

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“…6, D and E). It was previously shown in mice genetically predisposed to epithelial cell dysfunction that hyperoxia-induced oxidative stress accelerated the proliferation of Club cells in the bronchial epithelium (31). In our model, the in utero e-cig exposure may have increased the proliferation of Club cells when compared with the air control group.…”

Section: L716mentioning

confidence: 66%

“…In addition, the predominant cell type in the bronchial epithelium is the Club cell (117). Club cells are nonciliated secretory cells that play key functions in 1) regeneration of lung cells after injury, via Notch signaling-regulated differentiation into ciliated, goblet, and type II alveolar cells; 2) immunomodulation; and 3) detoxification (31,102). Using immunochemistry techniques, we found that uteroglobin expression, a protein secreted by bronchial Club cells, was significantly increased in the lung tissue of the preconception e-cig-exposed offspring (Fig.…”

Section: L716mentioning

confidence: 99%

In utero exposures to electronic-cigarette aerosols impair the Wnt signaling during mouse lung development

Noël

Hansen

Zaman

et al. 2020

American Journal of Physiology-Lung Cellular and Molecular Phys

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Currently, more than 9 million American adults, including women of childbearing age, use electronic-cigarettes (e-cigs). Further, the prevalence of maternal vaping now approaching 10% is similar to that of maternal smoking. Little, however, is known about the effects of fetal exposures to nicotine-rich e-cig aerosols on lung development. In this study, we assessed whether in utero exposures to e-cig aerosols compromised lung development in mice. A third-generation e-cig device was used to expose pregnant BALB/c mice by inhalation to 36 mg/mL of nicotine cinnamon-flavored e-cig aerosols for 14–31 days. This included exposures for either 12 days before mating plus during gestation (preconception groups) or only during gestation (prenatal groups). Respective control mice were exposed to filtered air. Subgroups of offspring were euthanized at birth or at 4 wk of age. Compared with respective air-exposed controls, both preconception and prenatal exposures to e-cig aerosols significantly decreased the offspring birth weight and body length. In the preconception group, 7 inflammation-related genes were downregulated, including 4 genes common to both dams and fetuses, denoting an e-cig immunosuppressive effect. Lung morphometry assessments of preconception e-cig-exposed offspring showed a significantly increased tissue fraction at birth. This result was supported by the downregulation of 75 lung genes involved in the Wnt signaling, which is essential to lung organogenesis. Thus, our data indicate that maternal vaping impairs pregnancy outcomes, alters fetal lung structure, and dysregulates the Wnt signaling. This study provides experimental evidence for future regulations of e-cig products for pregnant women and developmentally vulnerable populations.

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“…Oxidative stress and apoptosis are potential therapeutic targets of PF. Simply elicitation of oxidative stress is sufficient to induce PF in Atp8b1 mutant mice (4). Bleomycin (bleomycin) induced lung injury is the most commonly used model of PF (5).…”

Section: Introductionmentioning

confidence: 99%

Ligustilide modulates oxidative stress, apoptosis, and immunity to avoid pathological damages in bleomycin induced pulmonary fibrosis rats via inactivating TLR4/MyD88/NF-KB P65

et al. 2020

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Background: Pulmonary fibrosis (PF) is a fatal disease with increasing incidence. Ligustilide (LIG) has been shown to inhibit oxidative stress, apoptosis, and inflammation. Here we investigated the possible effect of LIG on bleomycin-induced PF in Sprague-Dawley rats.Methods: PF rats were set up through a single endotracheal injection of bleomycin (5 mg/kg). Then rats were treated with 20, 40, and 80 mg/kg LIG for four weeks, and the effects were estimated.Results: Overall, LIG significantly improved ventilation and reduced hyperplasia, and treatment of LIG reduced fibrosis as indicated by Masson staining and reduced expression of transforming growth factorbeta (TGF-β), Fibronectin, and alpha-smooth muscle actin (α-SMA). Oxidative stress was induced with bleomycin while inhibited with LIG, as showed with rebalanced serum lactate dehydrogenase (LDH), and tissue superoxide dismutase (SOD), glutathione peroxidase (GSH) and malondialdehyde (MDA). Apoptosis was further inhibited with LIG, as shown with Terminal dUTP nick-end labeling (TUNEL) staining and expression of Caspase-3, Caspase-9, Bax, and Bcl-2. Th1/Th2 balance was also rebuilt as evaluated with CD4 and IFNγ/IL-4 labeled flow cytometry of peripheral blood mononuclear cells (PBMCs) and expression of inducible nitric oxide synthase (iNOS) and IL-10 in the serum and lung. Protein expression of Toll-like receptor 4 (TLR4), HSP60-TLR4-myeloid differentiation factor 88 (Myd88) and nuclear factor-kappa B (NF-κB) p-P65/P65 was significantly reduced with LIG treatment. All the effects of LIG exhibited in a dosedependent way.Conclusions: LIG improved bleomycin-induced PF with improved ventilation, reduced fibroblast, reduced oxidative stress and apoptosis, and rebalanced Th1/Th2 immunity, through TLR4/MyD88/NF-κB P65 signaling.

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“…( 6) Eventually prolonged iatrogenic exposure to oxygen in combination with COVID-19 can exacerbate cell apoptosis at the alveolar epithelium level resulting into pulmonary fibrosis over an extended time period. (7) Lung tissues are protected by overactive immune mediated Adenosine A 2A receptor cells. These immune cells play a critical role in the down-regulation of pulmonary inflammation.…”

Section: Discussionmentioning

confidence: 99%

Oxygen: Friend or foe in the COVID-19 battle

Esmail¹

2021

Preprint

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“…Excessive oxygenation can cause the amount of ROS to exceed the required redox homeostasis leading to histologically progressive destruction of alveolocapillary membranes causing obstruction of capillaries forming microthrombi and air leaks via already injured alveoli into the surrounding tissues 6 . Eventually, prolonged iatrogenic exposure to oxygen in combination with COVID‐19 can exacerbate cell apoptosis at the alveolar epithelium level resulting in pulmonary fibrosis over an extended time period 7 …”

Section: Discussionmentioning

confidence: 99%