scholarly journals Function of cAMP scaffolds in obstructive lung disease: Focus on epithelial‐to‐mesenchymal transition and oxidative stress

2019 ◽  
Vol 176 (14) ◽  
pp. 2402-2415 ◽  
Author(s):  
Haoxiao Zuo ◽  
Isabella Cattani‐Cavalieri ◽  
Samuel Santos Valença ◽  
Nshunge Musheshe ◽  
Martina Schmidt
Keyword(s):  
Oxidative Stress ◽  
Lung Disease ◽  
Obstructive Lung Disease ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Disease Focus ◽  
And Oxidative Stress

Epithelial‐to‐Mesenchymal Transition and Oxidative Stress in Chronic Allograft Nephropathy

2005 ◽  
Vol 5 (3) ◽  
pp. 500-509 ◽  
Author(s):  
Arjang Djamali ◽  
Shannon Reese ◽  
Joseph Yracheta ◽  
Terry Oberley ◽  
Debra Hullett ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial To Mesenchymal Transition ◽  
Chronic Allograft Nephropathy ◽  
Mesenchymal Transition ◽  
And Oxidative Stress

scholarly journals Mechanisms and consequences of oxidative stress in lung disease: therapeutic implications for an aging populace

2018 ◽  
Vol 314 (4) ◽  
pp. L642-L653 ◽  
Author(s):  
Louise Hecker
Keyword(s):  
Oxidative Stress ◽  
Lung Disease ◽  
Lung Diseases ◽  
The Elderly ◽  
Therapeutic Strategies ◽  
Rapid Expansion ◽  
Pulmonary Diseases ◽  
Normal Lung ◽  
Incidence And Mortality ◽  
And Oxidative Stress

The rapid expansion of the elderly population has led to the recent epidemic of age-related diseases, including increased incidence and mortality of chronic and acute lung diseases. Numerous studies have implicated aging and oxidative stress in the pathogenesis of various pulmonary diseases; however, despite recent advances in these fields, the specific contributions of aging and oxidative stress remain elusive. This review will discuss the consequences of aging on lung morphology and physiology, and how redox imbalance with aging contributes to lung disease susceptibility. Here, we focus on three lung diseases for which aging is a significant risk factor: acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Preclinical and clinical development for redox- and senescence-altering therapeutic strategies are discussed, as well as scientific advancements that may direct current and future therapeutic development. A deeper understanding of how aging impacts normal lung function, redox balance, and injury-repair processes will inspire the development of new therapies to prevent and/or reverse age-associated pulmonary diseases, and ultimately increase health span and longevity. This review is intended to encourage basic, clinical, and translational research that will bridge knowledge gaps at the intersection of aging, oxidative stress, and lung disease to fuel the development of more effective therapeutic strategies for lung diseases that disproportionately afflict the elderly.

scholarly journals Malic enzyme 1 (ME1) in the biology of cancer: it is not just intermediary metabolism

2020 ◽  
Vol 65 (4) ◽  
pp. R77-R90
Author(s):  
Frank A Simmen ◽  
Iad Alhallak ◽  
Rosalia C M Simmen
Keyword(s):  
Oxidative Stress ◽  
Malic Enzyme ◽  
Epithelial To Mesenchymal Transition ◽  
Cholesterol Biosynthesis ◽  
Intermediary Metabolism ◽  
Therapeutic Approaches ◽  
Mesenchymal Transition ◽  
Epithelial Cancers ◽  
Transcriptional Target

Malic enzyme 1 (ME1) is a cytosolic protein that catalyzes the conversion of malate to pyruvate while concomitantly generating NADPH from NADP. Early studies identified ME1 as a mediator of intermediary metabolism primarily through its participatory roles in lipid and cholesterol biosynthesis. ME1 was one of the first identified insulin-regulated genes in liver and adipose and is a transcriptional target of thyroxine. Multiple studies have since documented that ME1 is pro-oncogenic in numerous epithelial cancers. In tumor cells, the reduction of ME1 gene expression or the inhibition of its activity resulted in decreases in proliferation, epithelial-to-mesenchymal transition and in vitro migration, and conversely, in promotion of oxidative stress, apoptosis and/or cellular senescence. Here, we integrate recent findings to highlight ME1’s role in oncogenesis, provide a rationale for its nexus with metabolic syndrome and diabetes, and raise the prospects of targeting the cytosolic NADPH network to improve therapeutic approaches against multiple cancers.

scholarly journals The Epithelial-to-Mesenchymal Transition (EMT) in the Development and Metastasis of Malignant Pleural Mesothelioma

2021 ◽  
Vol 22 (22) ◽  
pp. 12216
Author(s):  
Valeria Ramundo ◽  
Giada Zanirato ◽  
Elisabetta Aldieri
Keyword(s):  
Oxidative Stress ◽  
Malignant Pleural Mesothelioma ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Asbestos Exposure ◽  
Transforming Growth Factor Β ◽  
Pleural Mesothelioma ◽  
Mesenchymal Transition ◽  
Pharmacological Approach

Malignant pleural mesothelioma (MPM) is an aggressive tumor mainly associated with asbestos exposure and is characterized by a very difficult pharmacological approach. One of the molecular mechanisms associated with cancer onset and invasiveness is the epithelial-to-mesenchymal transition (EMT), an event induced by different types of inducers, such as transforming growth factor β (TGFβ), the main inducer of EMT, and oxidative stress. MPM development and metastasis have been correlated to EMT; On one hand, EMT mediates the effects exerted by asbestos fibers in the mesothelium, particularly via increased oxidative stress and TGFβ levels evoked by asbestos exposure, thus promoting a malignant phenotype, and on the other hand, MPM acquires invasiveness via the EMT event, as shown by an upregulation of mesenchymal markers or, although indirectly, some miRNAs or non-coding RNAs, all demonstrated to be involved in cancer onset and metastasis. This review aims to better describe how EMT is involved in driving the development and invasiveness of MPM, in an attempt to open new scenarios that are useful in the identification of predictive markers and to improve the pharmacological approach against this aggressive cancer.

scholarly journals Presence of Stromal Cells Enhances Epithelial-to-Mesenchymal Transition (EMT) Induction in Lung Bronchial Epithelium after Protracted Exposure to Oxidative Stress of Gamma Radiation

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Anna Acheva ◽  
Siamak Haghdoost ◽  
Alice Sollazzo ◽  
Virpi Launonen ◽  
Meerit Kämäräinen
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Dose Rate ◽  
Cell Lines ◽  
Stromal Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Low Dose ◽  
Mesenchymal Transition ◽  
Low Dose Rate ◽  
Stromal Component

The aim of the study was to investigate the role of a microenvironment in the induction of epithelial-to-mesenchymal transition (EMT) as a sign of early stages of carcinogenesis in human lung epithelial cell lines after protracted low-dose rateγ-radiation exposures. BEAS-2B and HBEC-3KT lung cell lines were irradiated with low-dose rateγ-rays (137Cs, 1.4 or 14 mGy/h) to 0.1 or 1 Gy with or without adding TGF-β. TGF-β-treated samples were applied as positive EMT controls and tested in parallel to find out if the radiation has a potentiating effect on the EMT induction. To evaluate the effect of the stromal component, the epithelial cells were irradiated in cocultures with stromal MRC-9 lung fibroblasts. On day 3 post treatment, the EMT markers:α-SMA, vimentin, fibronectin, and E-cadherin, were analyzed. The oxidative stress levels were evaluated by 8-oxo-dG analysis in both epithelial and fibroblast cells. The protracted exposure to low Linear Energy Transfer (LET) radiation at the total absorbed dose of 1 Gy was able to induce changes suggestive of EMT. The results show that the presence of the stromal component and its signaling (TGF-β) in the cocultures enhances the EMT. Radiation had a minor cumulative effect on the TGF-β-induced EMT with both doses. The oxidative stress levels were higher than the background in both epithelial and stromal cells post chronic irradiation (0.1 and 1 Gy); as for the BEAS-2B cell line, the increase was statistically significant. We suggest that the induction of EMT in bronchial epithelial cells by radiation requires more than single acute exposure and the presence of stromal component might enhance the effect through free radical production and accumulation.

scholarly journals Protective Effect of Yi Shen Pai Du Formula against Diabetic Kidney Injury via Inhibition of Oxidative Stress, Inflammation, and Epithelial-to-Mesenchymal Transition in db/db Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Qilin Zhang ◽  
Xiaocui Liu ◽  
Mitchell A. Sullivan ◽  
Chen Shi ◽  
Bin Deng
Keyword(s):  
Oxidative Stress ◽  
Kidney Disease ◽  
Nlrp3 Inflammasome ◽  
Epithelial To Mesenchymal Transition ◽  
Cell Model ◽  
Microvascular Complications ◽  
Fasting Blood Glucose ◽  
Diabetic Kidney ◽  
Mesenchymal Transition ◽  
Caspase 1

Objective. Diabetic kidney disease (DKD) is one of the most common chronic microvascular complications of diabetes; however, there remains a lack of effective therapeutic strategies. Yi Shen Pai Du Formula (YSPDF), a traditional Chinese medicine preparation, has been clinically used in treating chronic kidney disease (CKD) for more than 20 years. However, whether YSPDF has a therapeutic effect on DKD has not been studied. Methods. This study was conducted to investigate the effect of YSPDF administration on db/db mice, a model of type 2 diabetes that develops DKD, and reveal its underlying mechanism of action through a high glucose- (HG-) induced renal injury cell model. Results. We found that YSPDF significantly improved numerous biochemical parameters (fasting blood glucose, serum creatinine, blood urea nitrogen, 24 h urine total protein, total cholesterol, and total triglycerides) and ameliorated the abnormal histology and fibrosis of renal tissue. Moreover, the status of oxidative stress and levels of inflammatory cytokines (TNF-α, IL-6, IL-1β, and MCP-1) were markedly inhibited by YSPDF treatment. YSPDF treatment significantly mitigated renal fibrosis, with evidence suggesting that this was by inhibiting epithelial-to-mesenchymal transition (EMT) via suppression of the TGF-β1/Smad pathway. Interestingly, the expression of Nrf2, HO-1, and NQO1, proteins known to be associated with oxidative stress, were significantly increased upon administration of YSPDF. The levels of NLRP3 inflammasome proteins, including NLRP3, ASC, caspase-1, and cleaved caspase-1 were decreased in the YSPDF-treated group. Cell experiments showed that YSPDF inhibited EMT and the NLRP3 inflammasome in HG-exposed HK-2 cells, possibly via activation of Nrf2. Conclusion. Our study indicates that YSPDF may ameliorate renal damage in db/db mice via inhibition of oxidative stress, inflammation, and EMT, with the mechanism potentially being related to the activation of the Nrf2 pathway.

scholarly journals Vimentin is Required for Tumor Progression and Metastasis in a Mouse Model of Non-Small Cell Lung Cancer

2020 ◽  
Author(s):  
Alexandra L. Berr ◽  
Kristin Wiese ◽  
Gimena dos Santos ◽  
Jennifer M. Davis ◽  
Clarissa M. Koch ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lung Cancer ◽  
Mouse Model ◽  
Lung Adenocarcinoma ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Differential Expression Analysis ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Lung Cancer Metastasis

AbstractVimentin, a type III intermediate filament, is highly expressed in aggressive epithelial cancers and is associated with increased rates of metastasis. We show that vimentin is causally required for lung cancer metastasis using a genetic mouse model of lung adenocarcinoma (LSL-KrasG12D;Tp53fl/fl, termed KPV+/+) crossed with vimentin-null mice (thereby creating KPV−/− mice). Both KPV+/+ and KPV−/− mice developed lung tumors, yet KPV−/− mice had delayed tumorigenesis and prolonged survival. KPV+/+ cells implanted in the flank metastasized to the lung while KPV−/− cells did not, providing additional evidence that vimentin is required for metastasis. Differential expression analysis of RNA-seq data demonstrated that KPV−/− cells had suppressed expression of genes that drive epithelial-to-mesenchymal transition, migration, and invasion, processes that are critical to the metastatic cascade. Integrative metabolomic and transcriptomic analysis revealed altered glutaminolysis, with KPV−/− cells accumulating glutathione, leading to impaired cell motility in response to oxidative stress. Together, these results show that loss of vimentin impairs epithelial-to-mesenchymal transition and regulation of the oxidative stress response, resulting in decreased metastasis in murine lung adenocarcinoma.

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