scholarly journals Extracellular Matrix Component Remodeling in Respiratory Diseases: What Has Been Found in Clinical and Experimental Studies?

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 342 ◽  
Author(s):  
Juliana T. Ito ◽  
Juliana D. Lourenço ◽  
Renato F. Righetti ◽  
Iolanda F.L.C. Tibério ◽  
Carla M. Prado ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Lung Function ◽  
Respiratory Diseases ◽  
Structural Changes ◽  
Experimental Studies ◽  
Experimental Models ◽  
Airway Hyperreactivity ◽  
Chronic Obstructive ◽  
Ecm Remodeling ◽  
Inflammatory Conditions

Changes in extracellular matrix (ECM) components in the lungs are associated with the progression of respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory distress syndrome (ARDS). Experimental and clinical studies have revealed that structural changes in ECM components occur under chronic inflammatory conditions, and these changes are associated with impaired lung function. In bronchial asthma, elastic and collagen fiber remodeling, mostly in the airway walls, is associated with an increase in mucus secretion, leading to airway hyperreactivity. In COPD, changes in collagen subtypes I and III and elastin, interfere with the mechanical properties of the lungs, and are believed to play a pivotal role in decreased lung elasticity, during emphysema progression. In ARDS, interstitial edema is often accompanied by excessive deposition of fibronectin and collagen subtypes I and III, which can lead to respiratory failure in the intensive care unit. This review uses experimental models and human studies to describe how inflammatory conditions and ECM remodeling contribute to the loss of lung function in these respiratory diseases.

scholarly journals The Role of Changes in Extracellular Matrix of Cartilage in the Presence of Inflammation on the Pathology of Osteoarthritis

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Maricela Maldonado ◽  
Jin Nam
Keyword(s):  
Extracellular Matrix ◽  
Repair Process ◽  
Cellular Component ◽  
Ecm Remodeling ◽  
Multiple Factors ◽  
Inflammatory Conditions ◽  
Composition And Structure ◽  
Poor Understanding ◽  
Wear And Tear

Osteoarthritis (OA) is a degenerative disease that affects various tissues surrounding joints such as articular cartilage, subchondral bone, synovial membrane, and ligaments. No therapy is currently available to completely prevent the initiation or progression of the disease partly due to poor understanding of the mechanisms of the disease pathology. Cartilage is the main tissue afflicted by OA, and chondrocytes, the sole cellular component in the tissue, actively participate in the degeneration process. Multiple factors affect the development and progression of OA including inflammation that is sustained during the progression of the disease and alteration in biomechanical conditions due to wear and tear or trauma in cartilage. During the progression of OA, extracellular matrix (ECM) of cartilage is actively remodeled by chondrocytes under inflammatory conditions. This alteration of ECM, in turn, changes the biomechanical environment of chondrocytes, which further drives the progression of the disease in the presence of inflammation. The changes in ECM composition and structure also prevent participation of mesenchymal stem cells in the repair process by inhibiting their chondrogenic differentiation. This review focuses on how inflammation-induced ECM remodeling disturbs cellular activities to prevent self-regeneration of cartilage in the pathology of OA.

scholarly journals Cigarette smoke induction of S100A9 contributes to chronic obstructive pulmonary disease

2020 ◽  
Vol 319 (6) ◽  
pp. L1021-L1035
Author(s):  
Christopher Railwah ◽  
Alnardo Lora ◽  
Kanza Zahid ◽  
Hannah Goldenberg ◽  
Michael Campos ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Extracellular Matrix ◽  
Lung Function ◽  
Matrix Metalloproteinase ◽  
Pulmonary Disease ◽  
Cigarette Smoke ◽  
Lung Fibroblasts ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Acute And Chronic Exposure

S100 calcium-binding protein A9 (S100A9) is elevated in plasma and bronchoalveolar lavage fluid (BALF) of patients with chronic obstructive pulmonary disease (COPD), and aging enhances S100A9 expression in several tissues. Currently, the direct impact of S100A9-mediated signaling on lung function and within the aging lung is unknown. Here, we observed that elevated S100A9 levels in human BALF correlated with age. Elevated lung levels of S100A9 were higher in older mice compared with in young animals and coincided with pulmonary function changes. Both acute and chronic exposure to cigarette smoke enhanced S100A9 levels in age-matched mice. To examine the direct role of S100A9 on the development of COPD, S100a9−/− mice or mice administered paquinimod were exposed to chronic cigarette smoke. S100A9 depletion and inhibition attenuated the loss of lung function, pressure-volume loops, airway inflammation, lung compliance, and forced expiratory volume in 0.05 s/forced vital capacity, compared with age-matched wild-type or vehicle-administered animals. Loss of S100a9 signaling reduced cigarette smoke-induced airspace enlargement, alveolar remodeling, lung destruction, ERK and c-RAF phosphorylation, matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-9 (MMP-9), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and keratinocyte-derived chemokine (KC) release into the airways. Paquinimod administered to nonsmoked, aged animals reduced age-associated loss of lung function. Since fibroblasts play a major role in the production and maintenance of extracellular matrix in emphysema, primary lung fibroblasts were treated with the ERK inhibitor LY3214996 or the c-RAF inhibitor GW5074, resulting in less S100A9-induced MMP-3, MMP-9, MCP-1, IL-6, and IL-8. Silencing Toll-like receptor 4 (TLR4), receptor for advanced glycation endproducts (RAGE), or extracellular matrix metalloproteinase inducer (EMMPRIN) prevented S100A9-induced phosphorylation of ERK and c-RAF. Our data suggest that S100A9 signaling contributes to the progression of smoke-induced and age-related COPD.

scholarly journals Dietary influences on chronic obstructive lung disease and asthma: a review of the epidemiological evidence

1999 ◽  
Vol 58 (2) ◽  
pp. 309-319 ◽  
Author(s):  
Henriette A. Smit ◽  
Linda Grievink ◽  
Cora Tabak
Keyword(s):  
Fatty Acids ◽  
Lung Function ◽  
Beneficial Effect ◽  
Respiratory Symptoms ◽  
Experimental Studies ◽  
Chronic Obstructive ◽  
Epidemiological Evidence ◽  
Airway Reactivity ◽  
Asthma Patients ◽  
The Relationship

The epidemiological evidence for a relationship between diet and indicators of asthma and chronic obstructive pulmonary disease (COPD) is evaluated. The review focuses on the intake of Na,n−3 fatty acids, and antioxidant vitamins as well as fruit and vegetables. Experimental studies suggest that a high-Na diet has a small adverse effect on airway reactivity in asthma patients. However, observational studies provide no clear evidence that high Na intake has adverse effects on airway reactivity or asthma symptoms in open populations.n−3 Polyunsaturated fatty acids, which are present in fish oils, are metabolized into less broncho-constricting and inflammatory mediators thann−6 polyunsaturated fatty acids. Studies in the general adult population suggest that a high fish intake has a beneficial effect on lung function, but the relationship with respiratory symptoms and clinically-manifest asthma or COPD is less evident. Also, experimental studies in asthma patients have not demonstrated an improvement in asthma severity after supplementation with fish oil. Several studies showed a beneficial association between fruit and vegetable intake and lung function, but the relationship with respiratory symptoms and the clinically-manifest disease was less convincing. A similar pattern was found for vitamin C in relation to indicators of asthma and COPD, but there are still conflicting results with respect to vitamin E and β-carotene. In conclusion, the epidemiological evidence for a beneficial effect on indicators of asthma and COPD of eating fish, fruit and vegetables is increasing. However, the effectiveness of dietary supplementation in open-population samples is often not demonstrated. Several unresolved questions are raised, which should be addressed in future studies on the relationship between diet and respiratory disease.

Relationship between structural changes and hyperpolarized gas magnetic resonance imaging in chronic obstructive pulmonary disease using computational simulations with realistic alveolar geometry

2009 ◽  
Vol 367 (1896) ◽  
pp. 2347-2369 ◽  
Author(s):  
Michal Plotkowiak ◽  
Kelly Burrowes ◽  
Jan Wolber ◽  
Christopher Buckley ◽  
Robert Davies ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Lung Function ◽  
Structural Changes ◽  
Image Acquisition ◽  
Chronic Obstructive ◽  
Resonance Imaging ◽  
Apparent Diffusion Coefficients ◽  
Hyperpolarized Gas ◽  
Hyperpolarized Gas Mri

Both the development of accurate models of lung function and their quantitative validation can be significantly enhanced by the use of functional imaging techniques. The advent of hyperpolarized noble gas magnetic resonance imaging (MRI) technology has increased the amount of local, functional information we can obtain from the lung. In particular, application of 3 He to measure apparent diffusion coefficients has enabled some measure of lung microstructure and airspace size within the lung. Models mimicking image acquisition in hyperpolarized gas MRI can improve understanding of the relationship between image findings and lung structure, and can be used to improve the definition of imaging protocols. In this paper, we review the state of the art in hyperpolarized gas MRI modelling. We also present our own results, obtained using a Monte Carlo approach and a realistic alveolar sac geometry, which has previously been applied in functional lung studies. In this way, we demonstrate the potential for models combining lung function and image acquisition, which could provide valuable tools in both basic studies and clinical practice.

scholarly journals Aged Skeletal Muscle Retains the Ability to Remodel Extracellular Matrix for Degradation of Collagen Deposition after Muscle Injury

2021 ◽  
Vol 22 (4) ◽  
pp. 2123
Author(s):  
Wan-Jing Chen ◽  
I-Hsuan Lin ◽  
Chien-Wei Lee ◽  
Yi-Fan Chen
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Skeletal Muscles ◽  
Muscle Injury ◽  
Structural Changes ◽  
Transforming Growth Factor ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Collagen Deposition ◽  
Skeletal Muscle Function ◽  
Ecm Remodeling

Aging causes a decline in skeletal muscle function, resulting in a progressive loss of muscle mass, quality, and strength. A weak regenerative capacity is one of the critical causes of dysfunctional skeletal muscle in elderly individuals. The extracellular matrix (ECM) maintains the tissue framework structure in skeletal muscle. As shown by previous reports and our data, the gene expression of ECM components decreases with age, but the accumulation of collagen substantially increases in skeletal muscle. We examined the structural changes in ECM in aged skeletal muscle and found restricted ECM degradation. In aged skeletal muscles, several genes that maintain ECM structure, such as transforming growth factor β (TGF-β), tissue inhibitors of metalloproteinases (TIMPs), matrix metalloproteinases (MMPs), and cathepsins, were downregulated. Muscle injury can induce muscle repair and regeneration in young and adult skeletal muscles. Surprisingly, muscle injury could not only efficiently induce regeneration in aged skeletal muscle, but it could also activate ECM remodeling and the clearance of ECM deposition. These results will help elucidate the mechanisms of muscle fibrosis with age and develop innovative antifibrotic therapies to decrease excessive collagen deposition in aged muscle.

scholarly journals Role of Nrf2 and Its Activators in Respiratory Diseases

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Qinmei Liu ◽  
Yun Gao ◽  
Xinxin Ci
Keyword(s):  
Respiratory Diseases ◽  
Respiratory Infections ◽  
Redox Balance ◽  
Antioxidant Response ◽  
Experimental Models ◽  
26S Proteasome ◽  
Chronic Obstructive ◽  
Related Factor ◽  
Protective Effects ◽  
Obstructive Pulmonary Disease

Transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a major regulator of antioxidant response element- (ARE-) driven cytoprotective protein expression. The activation of Nrf2 signaling plays an essential role in preventing cells and tissues from injury induced by oxidative stress. Under the unstressed conditions, natural inhibitor of Nrf2, Kelch-like ECH-associated protein 1 (Keap1), traps Nrf2 in the cytoplasm and promotes the degradation of Nrf2 by the 26S proteasome. Nevertheless, stresses including highly oxidative microenvironments, impair the ability of Keap1 to target Nrf2 for ubiquitination and degradation, and induce newly synthesized Nrf2 to translocate to the nucleus to bind with ARE. Due to constant exposure to external environments, including diverse pollutants and other oxidants, the redox balance maintained by Nrf2 is fairly important to the airways. To date, researchers have discovered that Nrf2 deletion results in high susceptibility and severity of insults in various models of respiratory diseases, including bronchopulmonary dysplasia (BPD), respiratory infections, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), and lung cancer. Conversely, Nrf2 activation confers protective effects on these lung disorders. In the present review, we summarize Nrf2 involvement in the pathogenesis of the above respiratory diseases that have been identified by experimental models and human studies and describe the protective effects of Nrf2 inducers on these diseases.

scholarly journals Lung function and respiratory diseases in people with psychosis: Population-based study

2015 ◽  
Vol 207 (1) ◽  
pp. 37-45 ◽  
Author(s):  
Krista Partti ◽  
Tuula Vasankari ◽  
Merja Kanervisto ◽  
Jonna Perälä ◽  
Samuli I. Saarni ◽  
...  
Keyword(s):  
Lung Function ◽  
General Population ◽  
Chronic Bronchitis ◽  
Respiratory Diseases ◽  
Psychotic Disorders ◽  
Respiratory Health ◽  
Population Based ◽  
Chronic Obstructive ◽  
Serum Cotinine ◽  
Increased Risk

BackgroundThere is little information on lung function and respiratory diseases in people with psychosis.AimsTo compare the respiratory health of people with psychosis with that of the general population.MethodIn a nationally representative sample of 8028 adult Finns, lung function was measured by spirometry. Information on respiratory diseases and symptoms was collected. Smoking was quantified with serum cotinine levels. Psychotic disorders were diagnosed utilising the Structured Clinical Interview for DSM-IV (SCID-I) and medical records.ResultsParticipants with schizophrenia and other non-affective psychoses had significantly lower lung function values compared with the general population, and the association remained significant for schizophrenia after adjustment for smoking and other potential confounders. Schizophrenia was associated with increased odds of pneumonia (odds ratio (OR) = 4.9), chronic obstructive pulmonary disease (COPD, OR = 4.2) and chronic bronchitis (OR = 3.8); and with high cotinine levels.ConclusionsSchizophrenia is associated with impaired lung function and increased risk for pneumonia, COPD and chronic bronchitis.

scholarly journals Emphysema-Predominant COPD Had a Greater 5-Year Mortality and a Worse Annual Decline in Lung Function Than Airway Obstruction-Predominant COPD or Asthma at Initial Same Degree of Airflow Obstruction

Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1261
Author(s):  
Chang-Wei Lin ◽  
Hung-Yu Huang ◽  
Fu-Tsai Chung ◽  
Chun-Yu Lo ◽  
Yu-Chen Huang ◽  
...  
Keyword(s):  
Lung Function ◽  
Structural Changes ◽  
Airflow Obstruction ◽  
Airway Disease ◽  
Rank Test ◽  
Chronic Obstructive ◽  
High Resolution Computed Tomography ◽  
Kaplan Meier ◽  
Asthma Patients ◽  
Annual Decline

Background and Objectives: We studied whether the extent of exertional oxygen desaturation and emphysema could cause greater mortality in COPD and asthma independent of airflow obstruction. Materials and Methods: We performed a 5-year longitudinal observational study in COPD and asthma patients who matched for airflow obstruction severity. All subjects performed a 6-min walk test (6MWT) and high-resolution computed tomography (HRCT) and followed spirometry and oxygen saturation (SpO2) during the 6MWT every 3–6 months. Overall survival was recorded. Cumulative survival curves were performed according to the Kaplan–Meier method and compared with the log-rank test. Results: The COPD group had higher emphysema scores, higher Δinspiratory capacities (ICs) and lower SpO2 during the 6MWT, which showed a greater yearly decline in FEV1 (40.6 mL) and forced vital capacity (FVC) (28 mL) than the asthma group (FEV1, 9.6 mL; FVC, 1.2 mL; p < 0.05). The emphysema-predominant COPD group had an accelerated annual decline in lung function and worse survival. The nadir SpO2 ≤ 80% and a higher emphysema score were the strong risk factors for mortality in COPD patients. Conclusions: The greater structural changes with a higher emphysema score and greater desaturation during the 6MWT in COPD may contribute to worse yearly decline in FEV1 and higher five-year mortality than in asthma patients with a similar airflow obstruction. The lowest SpO2 ≤ 80% during the 6MWT and emphysema-predominant COPD were the strong independent factors for mortality in chronic obstructive airway disease patients.

METHODS FOR SIMULATION OF ACUTE BRAIN ISCHEMIA: PATHOPHYSIOLOGICAL SUBSTANTIATION OF SELECTION AND IMPORTANCE FOR CLINICAL PRACTICE

2019 ◽  
pp. 142-152
Author(s):  
Б.И. Гельцер ◽  
Э.В. Слабенко ◽  
Ю.В. Заяц ◽  
В.Н. Котельников
Keyword(s):  
Clinical Practice ◽  
Experimental Studies ◽  
Cerebrovascular Diseases ◽  
Experimental Models ◽  
Pathological Process ◽  
Ischemic Brain ◽  
Actual Clinical Practice ◽  
Acute Cerebral Ischemia ◽  
Different Types ◽  
Acute Brain Ischemia

Одним из основных требований к разработке экспериментальных моделей цереброваскулярных заболеваний является их максимальная приближенность к реальной клинической практике. В работе систематизированы данные по основным методам моделирования острой ишемии головного мозга (ОИГМ), представлена их классификация, анализируются данные о преимуществах и недостатках той или иной модели. Обсуждаются результаты экспериментальных исследований по изучению патогенеза ОИГМ с использованием различных моделей (полной и неполной глобальной, локальной и мультифокальной ишемии) и способов их реализации (перевязка артерий, клипирование, коагуляция, эмболизация и др.). Особое внимание уделяется «стабильности» последствий острого нарушения мозгового кровообращения: необратимых ишемических повреждений головного мозга или обратимых с реперфузией заданной продолжительности. Отмечается, что важное значение в этих исследованиях должно принадлежать современным методам прижизненной визуализации очагов острого ишемического повреждения, что позволяет оценивать динамику патологического процесса. Предлагаемый метод отвечает требованиям гуманного обращения с животными. Подчеркивается, что выбор релевантной модели ОИГМ определяется задачами предстоящего исследования и технологическими ресурсами научной лаборатории. Development of experimental models for acute forms of cerebrovascular diseases is essential for implementation of methods for their prevention and treatment. One of the principal requirements to such models is their maximum approximation to actual clinical practice. This review systematized major models of acute cerebral ischemia (ACI), their classification, and presented information about their advantages and shortcomings. Also, the review presented results of experimental studies on pathophysiological mechanisms of different types of modeled ACI (complete and incomplete global, local, and multifocal ischemia) and methods for creating these models (arterial ligation, clipping, coagulation, embolization, etc.). Particular attention was paid to “stability” of the consequences of acutely impaired cerebral circulation - an irreversible ischemic brain injury or a reversible injury with reperfusion of a given duration. The authors emphasized that in such studies, a special significance should be given to intravital imaging of acute ischemic damage foci using modern methods, which allow assessing the dynamics of the pathological process and meet the requirements to humane treatment of animals. The choice of a relevant ACI model is determined by objectives of the planned study and the technological resources available at the research laboratory.

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