Downregulation of NOX4 improves airway remodeling and inflammation by the TGF-β1-Smad2/3 pathway in asthma

Aili  Xuan,; Mei  Yang,; Qun  Xia,; Qian Sun,

doi:10.14715/cmb/2023.69.9.31

Cited by 3 publications

References 37 publications

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Multi-Trait Genetic Analysis of Asthma and Eosinophils Uncovers Novel Loci in East Asians

Chang,

Zhi,

Jiang

et al. 2024

Preprint

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Asthma is a prevalent respiratory condition with over 100 genetic loci identified through genome-wide association studies (GWAS). However, the genetic basis of asthma in East Asians remains underexplored. To address this, we performed a comprehensive analysis of shared genetic mechanisms between asthma and white blood cell (WBC) traits in East Asians, aiming to identify novel pleiotropic loci. Using linkage disequilibrium score regression (LDSC), we identified a significant genetic correlation between asthma and eosinophil count, further supported by Mendelian randomization (MR) analysis. A multi-trait analysis of GWAS (MTAG) uncovered 52 genome-wide significant loci, including 31 novel loci specific to East Asians. Notably, we discovered a missense variant (rs75326924) in the CD36 gene that exhibits increased expression in lymphocytes and ILC2-enriched cells in asthma patients, confirmed by flow cytometry. Proteomic profiling demonstrated downregulation of immune-related proteins such as Interleukin-7, Oncostatin M, and VEGFA in carriers of rs75326924, a variant previously associated with CD36 deficiency. Our findings provide insights into novel genetic loci and candidate genes underlying asthma in East Asians, offering potential targets for therapeutic interventions tailored to this population.

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Multi-Trait Genetic Analysis of Asthma and Eosinophils Uncovers Novel Loci in East Asians

Chang,

Zhi,

Jiang

et al. 2024

Preprint

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Cytoprotective Effects and Intranuclear Localization of Sulfur-Containing Derivative of Buckminsterfullerene

Kostyuk,

Malinovskaya,

Umriukhin

et al. 2024

Front. Biosci. (Landmark Ed)

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Background: There is a growing interest in exploring the biological characteristics of nanoparticles and exploring their potential applications. However, there is still a lack of research into the potential genotoxicity of fullerene derivatives and their impact on gene expression in human cells. In this study, we investigated the effects of a water-soluble fullerene derivative, C60[C6H4SCH2COOK]5H (F1), on human embryonic lung fibroblasts (HELF). Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was used to study the cytotoxicity of F1; reactive oxygen species (ROS) level was determined with 2,7-DCFH-DA; gene expression level was evaluated by reverse transcription polymerase chain reaction (RT-PCR); protein expression level was determined by flow cytofluorometry; fluorescence microscopy was used for visualization; Mann-Whitney statistical U-test was used for data processing. The differences were considered significant at p < 0.01. Results: F1 at a concentration of 0.3 mg/mL causes a short-term (up to 1 hour) increase in the number of double-strand breaks and oxidative DNA damage in HELF. Within 1 to 24 hours, F1 penetrates through the cell and nuclear membrane of HELF and localizes in the nucleus. In this case, the response of cells to DNA damage is activated: the functional activity of DNA repair genes, antioxidant and anti-apoptotic genes is increased within 24 hours. Due to the processes of activation of cell division and inhibition of apoptosis, an increase in the population of HELF cells in the presence of the fullerene derivative F1 is observed. F1 has a stabilizing effect on cell nuclei under the action of 1 Gy radiation. Conclusions: An increase in antioxidant protection, activation of repair genes, anti-apoptotic genes, progression of the cell cycle, and a decrease in the level of oxidative damage, and DNA breaks in cells indicates the cytoprotective properties of F1.

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The Role of Transforming Growth Factor-β (TGF-β) in Asthma and Chronic Obstructive Pulmonary Disease (COPD)

Kraik,

Tota,

Laska

et al. 2024

Cells

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Asthma and chronic obstructive pulmonary disease (COPD) represent chronic inflammatory respiratory disorders that, despite having distinct pathophysiological underpinnings, both feature airflow obstruction and respiratory symptoms. A critical component in the pathogenesis of each condition is the transforming growth factor-β (TGF-β), a multifunctional cytokine that exerts varying influences across these diseases. In asthma, TGF-β is significantly involved in airway remodeling, a key aspect marked by subepithelial fibrosis, hypertrophy of the smooth muscle, enhanced mucus production, and suppression of emphysema development. The cytokine facilitates collagen deposition and the proliferation of fibroblasts, which are crucial in the structural modifications within the airways. In contrast, the role of TGF-β in COPD is more ambiguous. It initially acts as a protective agent, fostering tissue repair and curbing inflammation. However, prolonged exposure to environmental factors such as cigarette smoke causes TGF-β signaling malfunction. Such dysregulation leads to abnormal tissue remodeling, marked by excessive collagen deposition, enlargement of airspaces, and, thus, accelerated development of emphysema. Additionally, TGF-β facilitates the epithelial-to-mesenchymal transition (EMT), a process contributing to the phenotypic alterations observed in COPD. A thorough comprehension of the multifaceted role of TGF-β in asthma and COPD is imperative for elaborating precise therapeutic interventions. We review several promising approaches that alter TGF-β signaling. Nevertheless, additional studies are essential to delineate further the specific mechanisms of TGF-β dysregulation and its potential therapeutic impacts in these chronic respiratory diseases.

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Downregulation of NOX4 improves airway remodeling and inflammation by the TGF-β1-Smad2/3 pathway in asthma

Cited by 3 publications

References 37 publications

Multi-Trait Genetic Analysis of Asthma and Eosinophils Uncovers Novel Loci in East Asians

Multi-Trait Genetic Analysis of Asthma and Eosinophils Uncovers Novel Loci in East Asians

Cytoprotective Effects and Intranuclear Localization of Sulfur-Containing Derivative of Buckminsterfullerene

The Role of Transforming Growth Factor-β (TGF-β) in Asthma and Chronic Obstructive Pulmonary Disease (COPD)

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