Mitochondrial network dynamics in pulmonary disease: Bridging the gap between inflammation, oxidative stress, and bioenergetics

Redox Biology, Год журнала: 2024, Номер 70, С. 103049 - 103049

Опубликована: Янв. 20, 2024

Once thought of in terms bioenergetics, mitochondria are now widely accepted as both the orchestrator cellular health and gatekeeper cell death. The pulmonary disease field has performed extensive efforts to explore role regulating inflammation, metabolism, apoptosis, oxidative stress. However, a critical component these processes needs be more studied: mitochondrial network dynamics. Mitochondria morphologically change response their environment regulate through fusion, fission, mitophagy. This allows adapt function respond requirements, maintaining homeostasis. For that reason, dynamics can considered bridge brings multiple together, revealing potential pathway for therapeutic intervention. In this review, we discuss modulators how they affected diseases, including chronic obstructive (COPD), idiopathic fibrosis (IPF), acute lung injury (ALI), arterial hypertension (PAH). A dysregulated plays crucial pathobiology, aberrant fission/fusion/mitophagy pathways druggable warrant further exploration. Thus, also candidates therapeutics

Язык: Английский

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Efficient intervention for pulmonary fibrosis via mitochondrial transfer promoted by mitochondrial biogenesis

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Сен. 18, 2023

The use of exogenous mitochondria to replenish damaged has been proposed as a strategy for the treatment pulmonary fibrosis. However, success this is partially restricted by difficulty supplying sufficient diseased cells. Herein, we report generation high-powered mesenchymal stem cells with promoted mitochondrial biogenesis and facilitated transfer injured lung sequential pioglitazone iron oxide nanoparticles. This highly efficient shown not only restore homeostasis but also reactivate inhibited mitophagy, consequently recovering impaired cellular functions. We perform studies in mouse show that these successfully mitigate fibrotic progression progressive fibrosis model, which was further verified humanized multicellular spheroid model. present findings provide potential overcome current limitations replenishment therapy, thereby promoting therapeutic applications intervention.

Язык: Английский

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Oxidative Stress and Air Pollution: Its Impact on Chronic Respiratory Diseases

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(1), С. 853 - 853

Опубликована: Янв. 3, 2023

Redox regulation participates in the control of various aspects metabolism. Reactive oxygen and nitrogen species participate many reactions under physiological conditions. When these overcome antioxidant defense system, a distressed status emerges, increasing biomolecular damage leading to functional alterations. Air pollution is one exogenous sources reactive species. Ambient airborne particulate matter (PM) important because its complex composition, which includes transition metals organic compounds. Once contact with lungs’ epithelium, PM components initiate synthesis inflammatory mediators, macrophage activation, modulation gene expression, activation transcription factors, are all related physiopathology chronic respiratory diseases, including cancer. Even though pathophysiological pathways that give rise development distress biological not fully understood, scientific evidence indicates redox-dependent signaling involved. This article presents an overview redox interaction air inside human body courses diseases.

Язык: Английский

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The lung mesenchyme in development, regeneration, and fibrosis

Journal of Clinical Investigation, Год журнала: 2023, Номер 133(14)

Опубликована: Июль 16, 2023

Mesenchymal cells are uniquely located at the interface between epithelial lining and stroma, allowing them to act as a signaling hub among diverse cellular compartments of lung. During embryonic postnatal lung development, mesenchyme-derived signals instruct budding, branching morphogenesis, subsequent structural functional maturation. Later during adult life, mesenchyme plays divergent roles wherein its balanced activation promotes repair after injury while aberrant can lead pathological remodeling fibrosis that associated with multiple chronic pulmonary diseases, including bronchopulmonary dysplasia, idiopathic fibrosis, obstructive disease. In this Review, we discuss involvement in various morphogenic, neomorphogenic, dysmorphogenic aspects biology health, special emphasis on fibroblast subsets smooth muscle cells, intercellular communication, intrinsic mesenchymal mechanisms drive such physiological pathophysiological events throughout homeostasis, repair, regeneration, aging.

Язык: Английский

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Matrine alleviates oxidative stress and ferroptosis in severe acute pancreatitis-induced acute lung injury by activating the UCP2/SIRT3/PGC1α pathway

International Immunopharmacology, Год журнала: 2023, Номер 117, С. 109981 - 109981

Опубликована: Март 8, 2023

Язык: Английский

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Targeting reprogrammed metabolism as a therapeutic approach for respiratory diseases

Biochemical Pharmacology, Год журнала: 2024, Номер 228, С. 116187 - 116187

Опубликована: Март 30, 2024

Metabolic reprogramming underlies the etiology and pathophysiology of respiratory diseases such as asthma, idiopathic pulmonary fibrosis (IPF), chronic obstructive disease (COPD). The dysregulated cellular activities driving airway inflammation remodelling in these have reportedly been linked to aberrant shifts energy-producing metabolic pathways: glycolysis oxidative phosphorylation (OXPHOS). rewiring OXPHOS accompanying therapeutic effects many clinical compounds natural products IPF, COPD, supports targeting metabolism a approach for diseases. Correspondingly, inhibiting has largely attested effective against experimental COPD. However, modulating its supporting catabolic pathways like mitochondrial pyruvate catabolism, fatty acid β-oxidation (FAO), glutaminolysis remain inconclusive. An emerging repertoire enzymes are also interconnected canonical that similarly possess potential Taken together, this review highlights urgent demand future studies ascertain role different diseases, under stimulatory conditions, cell types. While provides strong evidence support inhibition further verification by trials is definitely required.

Язык: Английский

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Mitochondrial uncoupling protein‐2 reprograms metabolism to induce oxidative stress and myofibroblast senescence in age‐associated lung fibrosis

Aging Cell, Год журнала: 2022, Номер 21(9)

Опубликована: Авг. 7, 2022

Mitochondrial dysfunction has been associated with age-related diseases, including idiopathic pulmonary fibrosis (IPF). We provide evidence that implicates chronic elevation of the mitochondrial anion carrier protein, uncoupling protein-2 (UCP2), in increased generation reactive oxygen species, altered redox state and cellular bioenergetics, impaired fatty acid oxidation, induction myofibroblast senescence. This pro-oxidant senescence reprogramming occurs concert conventional actions UCP2 as an uncoupler oxidative phosphorylation dissipation membrane potential. is highly expressed human IPF lung myofibroblasts aged fibroblasts. In aging murine model fibrosis, vivo silencing induces regression. These studies indicate a pro-fibrotic function disease support its therapeutic targeting diseases tissue regeneration organ fibrosis.

Язык: Английский

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Cellular Senescence: A Troy Horse in Pulmonary Fibrosis

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(22), С. 16410 - 16410

Опубликована: Ноя. 16, 2023

Pulmonary fibrosis (PF) is a chronic interstitial lung disease characterized by myofibroblast abnormal activation and extracellular matrix deposition. However, the pathogenesis of PF remains unclear, treatment options are limited. Epidemiological studies have shown that average age patients estimated to be over 65 years, incidence increases with age. Therefore, considered an age-related disease. A preliminary study on demonstrated combination therapy anti-senescence drugs dasatinib quercetin improved physical functional indicators. Given global aging population role cellular senescence in tissue organ aging, understanding impact growing interest. This article systematically summarizes causes signaling pathways PF. It also objectively analyzes AECs fibroblasts development. Furthermore, potential intervention methods targeting discussed. review not only provides strong theoretical foundation for manipulating senescence, developing new therapies improve diseases, extending healthy lifespan but offers hope reversing toxicity caused massive accumulation cells humans.

Язык: Английский

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Exercise mitigates age-related metabolic diseases by improving mitochondrial dysfunction

Ageing Research Reviews, Год журнала: 2023, Номер 91, С. 102087 - 102087

Опубликована: Окт. 11, 2023

Язык: Английский

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NADPH oxidase 4 is dispensable for skin myofibroblast differentiation and wound healing

Redox Biology, Год журнала: 2023, Номер 60, С. 102609 - 102609

Опубликована: Янв. 13, 2023

Differentiation of fibroblasts to myofibroblasts is governed by the transforming growth factor beta (TGF-β) through a mechanism involving redox signaling and generation reactive oxygen species (ROS). Myofibroblasts synthesize proteins extracellular matrix (ECM) display contractile phenotype. are predominant contributors wound healing several pathological states, including fibrotic diseases cancer. Inhibition ROS-generating enzyme NADPH oxidase 4 (NOX4) has been proposed mitigate fibroblast myofibroblast differentiation offer therapeutic option for treatment diseases. In this study, we addressed role NOX4 in physiological TGF-β-induced differentiation. We explored phenotypic changes induced TGF-β primary skin isolated from Nox4-deficient mice immunofluorescence, Western blotting RNA sequencing. Mice deficient Cyba, gene coding p22phox, key subunit were used confirmatory experiments as well human fibroblasts. vivo, was similar wild-type mice. vitro, despite strong upregulation following treatment, Nox4 did not influence although putative inhibitor GKT137831 flavoprotein diphenylene iodonium mitigated mechanism. Transcriptomic analysis revealed mitochondrial protein Ucp2 stress-response Hddc3 fibroblasts, which had however no impact on bioenergetics. Altogether, provide extensive evidence that dispensable differentiation, suggest another H2O2-generating drives

Язык: Английский

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