Peroxiredoxin-6 is a Guardian of lung pathophysiologies

2021 ◽  
Vol 22 ◽  
Author(s):  
Anju Kumari ◽  
Rimpy Kaur Chowhan ◽  
Pushpa Kakchingtabam ◽  
Sharifun Shahnaj ◽  
Hamidur Rahaman ◽  
...  
Keyword(s):  
Drug Target ◽  
Lung Diseases ◽  
Lung Surfactant ◽  
Normal Lung ◽  
Acyl Transferase ◽  
Phospholipase Activity ◽  
Peroxiredoxin 6 ◽  
Common Drug ◽  
Anti Oxidant ◽  
Important Enzyme

: The moonlighting protein, Prdx6 exhibits peroxidase activity, phospholipase activity and lysophosphatidylcholine acyl transferase (LPCAT) activity. Although it is ubiquitous in expression, its level is prominently high in the lung. Prdx6 has been known to be an important enzyme for the maintenance of normal lung physiologies including, anti-oxidant defense, lung surfactant homeostasis and cell signaling. Studies further unveiled that the altered activity (peroxidase or aiPLA2) of this enzyme is linked with various lung pathologies or diseases. In the present article, we attempted to address the various pathophysiologies or disease conditions (like lung ischemia, hyperoxia, lung cancer, emphysema and acute lung injury) wherein prdx6 is involved. The study implicates that Prdx6 could be used as a common drug target for multiple lung diseases. Important future insights have also been incorporated.

scholarly journals Unique Aspects of the Developing Lung Circulation: Structural Development and Regulation of Vasomotor Tone

2016 ◽  
Vol 6 (4) ◽  
pp. 407-425 ◽  
Author(s):  
Yuangsheng Gao ◽  
David N. Cornfield ◽  
Kurt R. Stenmark ◽  
Bernard Thébaud ◽  
Steven H. Abman ◽  
...  
Keyword(s):  
Lung Development ◽  
Lung Diseases ◽  
Vascular Tone ◽  
Current Knowledge ◽  
Normal Lung ◽  
Pulmonary Vasculature ◽  
Structural Development ◽  
Vasomotor Tone ◽  
Disease States ◽  
Vasculogenesis And Angiogenesis

This review summarizes our current knowledge on lung vasculogenesis and angiogenesis during normal lung development and the regulation of fetal and postnatal pulmonary vascular tone. In comparison to that of the adult, the pulmonary circulation of the fetus and newborn displays many unique characteristics. Moreover, altered development of pulmonary vasculature plays a more prominent role in compromised pulmonary vasoreactivity than in the adult. Clinically, a better understanding of the developmental changes in pulmonary vasculature and vasomotor tone and the mechanisms that are disrupted in disease states can lead to the development of new therapies for lung diseases characterized by impaired alveolar structure and pulmonary hypertension.

scholarly journals Poor Cognitive Function Is Associated with Obstructive Lung Diseases in Taiwanese Adults

2021 ◽  
Vol 18 (5) ◽  
pp. 2344
Author(s):  
Sun-Wung Hsieh ◽  
Da-Wei Wu ◽  
Chih-Wen Wang ◽  
Szu-Chia Chen ◽  
Chih-Hsing Hung ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Lung Function ◽  
Lung Diseases ◽  
Mmse Score ◽  
Multivariable Analysis ◽  
Forced Expiratory Volume ◽  
Normal Lung ◽  
Obstructive Lung Diseases ◽  
Normal Lung Function ◽  
Function Group

Previous studies have reported an association between the impairment of cognitive performance and lung diseases. However, whether obstructive or restrictive lung diseases have an impact on cognitive function is still inconclusive. We aimed to investigate the association between cognitive function and obstructive or restrictive lung diseases in Taiwanese adults using the Mini-Mental State Examination (MMSE). In this study, we used data from the Taiwan Biobank. Cognitive function was evaluated using the MMSE. Spirometry measurements of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained to assess lung function. Participants were classified into three groups according to lung function, namely, normal, restrictive, and obstructive lung function. In total, 683 patients enrolled, of whom 357 participants had normal lung function (52.3%), 95 had restrictive lung function (13.9%), and 231 had obstructive lung function (33.8%). Compared to the normal lung function group, the obstructive lung function group was associated with a higher percentage of cognitive impairment (MMSE < 24). In multivariable analysis, a low MMSE score was significantly associated with low FVC, low FEV1, and low FEV1/FVC. Furthermore, a low MMSE score was significantly associated with low FEV1 in the participants with FEV1/FVC < 70%, whereas MMSE was not significantly associated with FVC in the participants with FEV1/FVC ≥ 70%. Our results showed that a low MMSE score was associated with low FEV1, low FVC and low FEV1/FVC. Furthermore, a low MMSE score was associated with obstructive lung diseases but not with restrictive lung diseases.

scholarly journals In vitro models of fetal lung development to enhance research into congenital lung diseases

2021 ◽  
Author(s):  
Soichi Shibuya ◽  
Jessica Allen-Hyttinen ◽  
Paolo De Coppi ◽  
Federica Michielin
Keyword(s):  
Lung Development ◽  
Lung Diseases ◽  
Ex Vivo ◽  
Fetal Lung ◽  
Branching Morphogenesis ◽  
In Vitro Models ◽  
Normal Lung ◽  
Novel Therapeutic Strategies ◽  
Pseudoglandular Stage

Abstract Purpose This paper aims to build upon previous work to definitively establish in vitro models of murine pseudoglandular stage lung development. These can be easily translated to human fetal lung samples to allow the investigation of lung development in physiologic and pathologic conditions. Methods Lungs were harvested from mouse embryos at E12.5 and cultured in three different settings, i.e., whole lung culture, mesenchyme-free epithelium culture, and organoid culture. For the whole lung culture, extracted lungs were embedded in Matrigel and incubated on permeable filters. Separately, distal epithelial tips were isolated by firstly removing mesothelial and mesenchymal cells, and then severing the tips from the airway tubes. These were then cultured either in branch-promoting or self-renewing conditions. Results Cultured whole lungs underwent branching morphogenesis similarly to native lungs. Real-time qPCR analysis demonstrated expression of key genes essential for lung bud formation. The culture condition for epithelial tips was optimized by testing different concentrations of FGF10 and CHIR99021 and evaluating branching formation. The epithelial rudiments in self-renewing conditions formed spherical 3D structures with homogeneous Sox9 expression. Conclusion We report efficient protocols for ex vivo culture systems of pseudoglandular stage mouse embryonic lungs. These models can be applied to human samples and could be useful to paediatric surgeons to investigate normal lung development, understand the pathogenesis of congenital lung diseases, and explore novel therapeutic strategies.

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 Identification of biomarkers in common chronic lung diseases by co-expression networks and drug-target interactions analysis

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Mazaher Maghsoudloo ◽  
Sadegh Azimzadeh Jamalkandi ◽  
Ali Najafi ◽  
Ali Masoudi-Nejad
Keyword(s):  
Drug Target ◽  
Lung Diseases ◽  
Chronic Lung Diseases

scholarly journals Computational Modelling of the Interaction of Gold Nanoparticle with Lung Surfactant Monolayer

MRS Advances ◽  
2019 ◽  
Vol 4 (20) ◽  
pp. 1177-1185 ◽  
Author(s):  
Sheikh I. Hossain ◽  
Neha S. Gandhi ◽  
Zak E. Hughes ◽  
Suvash C. Saha
Keyword(s):  
Respiratory Diseases ◽  
Lung Surfactant ◽  
Computational Modelling ◽  
Fine Tuning ◽  
Coarse Grained ◽  
Normal Lung ◽  
Open Questions ◽  
Compression And Expansion ◽  
Modelling Studies ◽  
Dynamics Simulations

ABSTRACTLung surfactant (LS), a thin layer of phospholipids and proteins inside the alveolus of the lung is the first biological barrier to inhaled nanoparticles (NPs). LS stabilizes and protects the alveolus during its continuous compression and expansion by fine-tuning the surface tension at the air-water interface. Previous modelling studies have reported the biophysical function of LS monolayer and its role, but many open questions regarding the consequences and interactions of airborne nano-sized particles with LS monolayer remain. In spite of gold nanoparticles (AuNPs) having a paramount role in biomedical applications, the understanding of the interactions between bare AuNPs (as pollutants) and LS monolayer components still unresolved. Continuous inhalation of NPs increases the possibility of lung ageing, reducing the normal lung functioning and promoting lung malfunction, and may induce serious lung diseases such as asthma, lung cancer, acute respiratory distress syndrome, and more. Different medical studies have shown that AuNPs can disrupt the routine lung functions of gold miners and promote respiratory diseases. In this work, coarse-grained molecular dynamics simulations are performed to gain an understanding of the interactions between bare AuNPs and LS monolayer components at the nanoscale. Different surface tensions of the monolayer are used to mimic the biological process of breathing (inhalation and exhalation). It is found that the NP affects the structure and packing of the lipids by disordering lipid tails. Overall, the analysed results suggest that bare AuNPs impede the normal biophysical function of the lung, a finding that has beneficial consequences to the potential development of treatments of various respiratory diseases.

scholarly journals The Association between MUC5B Rs35705950 and Risks of Idiopathic Interstitial Pneumonia, Systemic Sclerosis Interstitial Lung Disease, and Familial Interstitial Pneumonia: A Meta-Analysis

2020 ◽  
Author(s):  
Huai-Qing LOU ◽  
Chun-Xia HUANG ◽  
Guang-Yi LI ◽  
Ping LI ◽  
Shou-Ming ZHANG ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Interstitial Pneumonia ◽  
Lung Diseases ◽  
Meta Analysis ◽  
Biomedical Literature ◽  
Idiopathic Interstitial Pneumonia ◽  
Normal Lung ◽  
Cochrane Central Register

Background: Interstitial lung disease (ILD) is a category of chronic lung diseases with more than 200 subtypes. Idiopathic interstitial pneumonia (IIP), systemic sclerosis (SSc) ILD, and familial interstitial pneumonia (FIP) are three major groups of lung diseases with different causes or with unknown causes. Mucin5B (MUC5B) belongs to the mucin family, which contribute to the lubricating and viscoelastic properties of the whole saliva, normal lung mucus, and cervical mucus. The association between MUC5B rs35705950 and ILDs risks has been widely studied. However, the results were inconclusive and inconsistent. Methods: In the present meta-analysis, the database PubMed, Embase, Cochrane Central Register of Controlled Trials, CNKI and Chinese Biomedical Literature Database were searched till Aug 20th, 2018. Overall 16 publications with 28 studies, 76345 cases and 18402 controls were included. Results: The results indicated a significant increase of overall IIP risk for TT genotype and T allele of the rs35705950 in all genetic models (TT vs GG, OR=9.11; TT vs GT+TT, OR=5.80; GT+TT vs GG, OR=4.34; T vs G, OR=4.03. P<0.0001). Subgroup analysis by subtypes of IIP revealed higher risks of TT genotype and T allele for IPF and iNSIP (P<0.05). A significant increase of FIP risk was also found for the TT genotype and T allele of the rs35705950 (TT vs GG, OR=17.08; GT+TT vs GG, OR=6.02; T vs G, OR=1.64.P<0.05). Conclusion: No significant relations existed between the rs35705950 and SSc-ILD risks. MUC5B rs35705950 might be a predictor for the susceptibility of IIP and FIP.

Apoprotein-based synthetic surfactants inhibit plasmic cleavage of fibrinogen in vitro

1993 ◽  
Vol 265 (2) ◽  
pp. L186-L192 ◽  
Author(s):  
A. Gunther ◽  
H. Bleyl ◽  
W. Seeger
Keyword(s):  
Lung Diseases ◽  
Polyacrylamide Gel Electrophoresis ◽  
Lung Surfactant ◽  
Sodium Dodecyl ◽  
Plasminogen Activator Inhibitor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Plasmin Activity ◽  
Inhibitory Capacity ◽  
Synthetic Surfactants

Fibrinogen (Fbg) leakage and intra-alveolar fibrin accumulation are commonly noticed in adult respiratory distress syndrome and interstitial lung diseases. Activation of the extrinsic coagulation pathway and elevation of antiplasmin- and plasminogen-activator inhibitor levels are assumed to favor alveolar clot formation and to inhibit fibrinolysis under these conditions. We investigated the influence of synthetic surfactants on the plasmic cleavage of fibrinogen in vitro. Fibrinogenolysis was quantified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with densitometric evaluation and fragment E enzyme-linked immunosorbent assay. A synthetic phospholipid mixture (PLM) (dipalmitoyl-DL-alpha-phosphatidylcholine:L-alpha-phosphatidyl-DL-gly cer ol: palmitic acid 68.5:22.5:9) caused a dose-dependent inhibition of fibrinogenolysis in a concentration range between 0.1 and 2 mg/ml. This inhibitory capacity was markedly amplified upon reconstitution of PLM with natural and recombinant surfactant protein (SP)-C as well as natural SP-B. Natural SP-A and recombinant SP-A were far less effective in this respect. In the absence of phospholipids, the hydrophobic apoproteins revealed only moderate plasmin inhibitory capacity (recombinant SP-C > natural SP-C and SP-B). Natural calf lung surfactant extract displayed comparable inhibitory capacity on plasmic Fbg cleavage as PLM. We conclude that hydrophobic surfactant material may suppress plasmin activity and thus may contribute to the finding of delayed alveolar fibrin clearance in inflammatory lung diseases with Fbg leakage.

scholarly journals The serpentine path to a novel mechanism-based inhibitor of acute inflammatory lung injury

2014 ◽  
Vol 116 (12) ◽  
pp. 1521-1530 ◽  
Author(s):  
Aron B. Fisher
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Oxidant Stress ◽  
Lung Surfactant ◽  
Phospholipase A ◽  
Peroxiredoxin 6 ◽  
The Past ◽  
Research Activities ◽  
Novel Target ◽  
Nadph Oxidase Activation

The Comroe lecture on which this review is based described my research path during the past 45 years, beginning with studies of oxidant stress (hyperoxia) and eventuating in the discovery of a synthetic inhibitor of phospholipase A2activity (called MJ33) that prevents acute lung injury in mice exposed to lipopolysaccharide. In between were studies of lung ischemia, lung surfactant metabolism, the protein peroxiredoxin 6 and its phospholipase A2activity, and mechanisms for NADPH oxidase activation. These seemingly unrelated research activities provided the nexus for identification of a novel target and a potentially novel therapeutic agent for prevention or treatment of acute lung injury.

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