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Acta Medica Indonesiana Apr 2021Pulmonary fibrosis due to COVID-19 is recognized as sequel of ARDS characterized by failed alveolar re-epithelization, fibroblast activation, excessive collagen... (Review)
Review
Pulmonary fibrosis due to COVID-19 is recognized as sequel of ARDS characterized by failed alveolar re-epithelization, fibroblast activation, excessive collagen deposition and other extracellular matrix components that disrupt the normal lung architecture. There are risk factor for pulmonary fibrosis namely advanced age, severe ARDS infection, mechanical ventilation due to ventilator-induced lung injury, smoking and chronic alcoholism. Diagnosis of post-COVID pulmonary fibrosis can be made by clinical symptoms and characteristic finding from lung CT scan. To date, there is no definitive treatment for post-inflammatory pulmonary fibrosis after COVID-19 infection, however some of antifibrotic therapies may be considered. Beside medical treatment, pulmonary rehabilitation program and long-term oxygen treatment should be included as part of comprehensive treatment for pulmonary fibrosis due to COVID-19.
Topics: COVID-19; Combined Modality Therapy; Humans; Pneumonia, Viral; Pulmonary Fibrosis; Risk Factors; SARS-CoV-2; Tomography, X-Ray Computed
PubMed: 34251354
DOI: No ID Found -
Journal of Ethnopharmacology Nov 2023Pulmonary fibrosis (PF) is a persistent and refractory illness accompanied by inflammation and fibrosis. Gracillin, a natural steroidal saponin, is one of the components...
ETHNOPHARMACOLOGICAL RELEVANCE
Pulmonary fibrosis (PF) is a persistent and refractory illness accompanied by inflammation and fibrosis. Gracillin, a natural steroidal saponin, is one of the components of Dioscorea quinqueloba which has been used in herbal medicines for treating some inflammatory diseases. Therefore, it may be a potential drug candidate for PF management.
AIM OF THE STUDY
This study aims to elucidate and verify the anti-pulmonary fibrosis effect of gracillin.
METHODS
We established an in vivo model of PF by treatment of mice with bleomycin (BLM) and an in vitro model by treatment of NIH-3T3 cells with TGF-β1. Pathological changes to the structure of lung tissue, pulmonary function, inflammatory exudation of bronchoalveolar lavage fluid (BALF) and deposition of collagen were detected in vivo, and extracellular matrix (ECM) deposition and migration were evaluated in vitro. The significance of gracillin on STAT3 phosphorylation and nuclear translocation were evaluated by western blotting, immunohistochemistry and immunofluorescence assays. The STAT3 transcriptional activity was quantified with a dual-luciferase reporter assay. Recovery experiments were performed by plasmid-directed overexpression of STAT3.
RESULTS
We found that gracillin could improve pulmonary function, reduce lung inflammation and mitigate collagen deposition to ameliorate BLM-induced PF in mice. Gracillin also suppressed TGF-β1-induced increases in ECM deposition biomarkers, including COL1A1, fibronectin, α-SMA, N-cad and vimentin, and repressed migration in NIH-3T3 cells. Additionally, gracillin suppressed the phosphorylation, nuclear translocation and transcriptional action of STAT3. Furthermore, the decreased ECM deposition and migration upon gracillin treatment were abrogated upon overexpression of STAT3 in NIH-3T3 cells.
CONCLUSIONS
Gracillin protects against PF by inhibiting the STAT3 axis, providing a safe and efficacious approach to treating PF.
Topics: Mice; Animals; Transforming Growth Factor beta1; Pulmonary Fibrosis; Lung; Collagen; Bleomycin
PubMed: 37257706
DOI: 10.1016/j.jep.2023.116704 -
Biomedicine & Pharmacotherapy =... Oct 2023Fibrotic extracellular matrix (ECM) remodeling characterized different types of pulmonary fibrosis, and its regulation could be a potential shared treatment strategy for...
BACKGROUND
Fibrotic extracellular matrix (ECM) remodeling characterized different types of pulmonary fibrosis, and its regulation could be a potential shared treatment strategy for pulmonary fibrosis.
PURPOSE
We aimed to investigate the effect of triptolide on pulmonary fibrosis through the inhibition of several important aspects of fibrotic ECM remodeling.
METHODS
Bleomycin-induced pulmonary fibrosis mice and TGF-β-induced primary lung fibroblasts were used. The effect of triptolide on pulmonary fibrosis was detected using histopathology, immunostaining, RT-qPCR, western blotting, ELISA, and protein activity assay.
RESULTS
Triptolide significantly alleviated bleomycin-induced pulmonary fibrosis in mice. It inhibited the expression of fibrotic genes α-SMA, collagen I, fibronectin, and vimentin and blocked the TGF-β-SMAD signaling pathway both in vivo and in vitro. In addition, triptolide regulated the expression and activity of MMPs during fibrosis. Interestingly, it suppressed the expression of lysyl oxidase, which was responsible for matrix cross-linking and elevated ECM stiffness. Furthermore, triptolide blocked the biomechanical stress transduction pathway integrin-β1-FAK-YAP signaling and attenuated the pro-fibrotic feedback of fibrotic ECM on fibroblasts via integrin inhibition.
CONCLUSION
These findings show that triptolide prevents the key linkages of fibrotic ECM remodeling, including deposition, degradation, cross-linking, and pro-fibrotic feedback and, therefore, has potential therapeutic value for pulmonary fibrosis.
Topics: Animals; Mice; Bleomycin; Extracellular Matrix; Integrins; Protein-Lysine 6-Oxidase; Pulmonary Fibrosis; Transforming Growth Factor beta; Matrix Metalloproteinases
PubMed: 37660647
DOI: 10.1016/j.biopha.2023.115394 -
European Respiratory Review : An... Jan 2024Molecular pathways found to be important in pulmonary fibrosis are also involved in cancer pathogenesis, suggesting common pathways in the development of pulmonary... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Molecular pathways found to be important in pulmonary fibrosis are also involved in cancer pathogenesis, suggesting common pathways in the development of pulmonary fibrosis and lung cancer.
RESEARCH QUESTION
Is pulmonary fibrosis from exposure to occupational carcinogens an independent risk factor for lung cancer?
STUDY DESIGN AND METHODS
A comprehensive search of PubMed, Embase, Web of Science and Cochrane databases with over 100 search terms regarding occupational hazards causing pulmonary fibrosis was conducted. After screening and extraction, quality of evidence and eligibility criteria for meta-analysis were assessed. Meta-analysis was performed using a random-effects model.
RESULTS
52 studies were identified for systematic review. Meta-analysis of subgroups identified silicosis as a risk factor for lung cancer when investigating odds ratios for silicosis in autopsy studies (OR 1.47, 95% CI 1.13-1.90) and for lung cancer mortality in patients with silicosis (OR 3.21, 95% CI 2.67-3.87). Only considering studies with an adjustment for smoking as a confounder identified a significant increase in lung cancer risk (OR 1.58, 95% CI 1.34-1.87). However, due to a lack of studies including cumulative exposure, no adjustments could be included. In a qualitative review, no definitive conclusion could be reached for asbestosis and silicosis as independent risk factors for lung cancer, partly because the studies did not take cumulative exposure into account.
INTERPRETATION
This systematic review confirms the current knowledge regarding asbestosis and silicosis, indicating a higher risk of lung cancer in exposed individuals compared to exposed workers without fibrosis. These individuals should be monitored for lung cancer, especially when asbestosis or silicosis is present.
Topics: Humans; Silicon Dioxide; Lung Neoplasms; Pulmonary Fibrosis; Asbestosis; Silicosis; Occupational Exposure
PubMed: 38355151
DOI: 10.1183/16000617.0224-2023 -
Journal of Nanobiotechnology Jul 2023It is reported that pulmonary fibrosis has become one of the major long-term complications of COVID-19, even in asymptomatic individuals. Currently, despite the best... (Review)
Review
It is reported that pulmonary fibrosis has become one of the major long-term complications of COVID-19, even in asymptomatic individuals. Currently, despite the best efforts of the global medical community, there are no treatments for COVID-induced pulmonary fibrosis. Recently, inhalable nanocarriers have received more attention due to their ability to improve the solubility of insoluble drugs, penetrate biological barriers of the lungs and target fibrotic tissues in the lungs. The inhalation route has many advantages as a non-invasive method of administration and the local delivery of anti-fibrosis agents to fibrotic tissues like direct to the lesion from the respiratory system, high delivery efficiency, low systemic toxicity, low therapeutic dose and more stable dosage forms. In addition, the lung has low biometabolic enzyme activity and no hepatic first-pass effect, so the drug is rapidly absorbed after pulmonary administration, which can significantly improve the bioavailability of the drug. This paper summary the pathogenesis and current treatment of pulmonary fibrosis and reviews various inhalable systems for drug delivery in the treatment of pulmonary fibrosis, including lipid-based nanocarriers, nanovesicles, polymeric nanocarriers, protein nanocarriers, nanosuspensions, nanoparticles, gold nanoparticles and hydrogel, which provides a theoretical basis for finding new strategies for the treatment of pulmonary fibrosis and clinical rational drug use.
Topics: Humans; Pulmonary Fibrosis; Gold; Administration, Inhalation; COVID-19; Metal Nanoparticles; Drug Delivery Systems; Lung; Pharmaceutical Preparations; Nanoparticles
PubMed: 37422665
DOI: 10.1186/s12951-023-01971-7 -
Biomedicine & Pharmacotherapy =... Oct 2023Lung injury and pulmonary fibrosis contribute to morbidity and mortality, and, in particular, are characterized as leading cause on confirmed COVID-19 death. To date,...
Lung injury and pulmonary fibrosis contribute to morbidity and mortality, and, in particular, are characterized as leading cause on confirmed COVID-19 death. To date, efficient therapeutic approach for such lung diseases is lacking. N-Acetylglucosamine (NAG), an acetylated derivative of glucosamine, has been proposed as a potential protector of lung function in several types of lung diseases. The mechanism by which NAG protects against lung injury, however, remains unclear. Here, we show that NAG treatment improves pulmonary function in bleomycin (BLM)-induced lung injury model measured by flexiVent system. At early phase of lung injury, NAG treatment results in silenced immune response by targeting ARG1 macrophages activation, and, consequently, blocks KRT8 transitional stem cell in the alveolar region to stimulate PDGF Rβ fibroblasts hyperproliferation, thereby attenuating the pulmonary fibrosis. This combinational depression of immune response and extracellular matrix deposition within the lung mitigates lung injury and pulmonary fibrosis induced by BLM. Our findings provide novel insight into the protective role of NAG in lung injury.
Topics: Humans; Pulmonary Fibrosis; Lung Injury; Acetylglucosamine; Bleomycin; COVID-19
PubMed: 37633052
DOI: 10.1016/j.biopha.2023.115069 -
Respirology (Carlton, Vic.) Jan 2022
Topics: Humans; Idiopathic Pulmonary Fibrosis; Lung; Lung Diseases, Interstitial
PubMed: 34846086
DOI: 10.1111/resp.14189 -
International Immunology Nov 2021Pulmonary fibrosis is caused by the interplay between genetic and environmental factors. Recent studies have revealed various genes associated with idiopathic pulmonary... (Review)
Review
Pulmonary fibrosis is caused by the interplay between genetic and environmental factors. Recent studies have revealed various genes associated with idiopathic pulmonary fibrosis, as well as the causative genes for familial pulmonary fibrosis. Although increased death or dysfunction of type 2 alveolar epithelial (AT2) cells has been detected in lung specimens from pulmonary fibrosis patients, it remains unclear whether and how AT2 cell death or dysfunction is responsible for the progression of pulmonary fibrosis. A recent study showed that increased AT2 cell necroptosis is the initial event in pulmonary fibrosis by analyzing patients with familial pulmonary fibrosis and an animal model that harbors the same mutation as patients. The contribution of AT2 cell necroptosis to the pathogenesis of pulmonary fibrosis has not been identified in animal model studies, which validates the effectiveness of genetic analysis of familial diseases to uncover unknown pathogeneses. Thus, further extensive genetic studies of pulmonary fibrosis along with functional studies based on genetic analysis will be crucial not only in elucidating the precise disease process but also, ultimately, in identifying novel treatment strategies for both familial and non-familial pulmonary fibrosis.
Topics: Animals; Disease Models, Animal; Idiopathic Pulmonary Fibrosis
PubMed: 34049386
DOI: 10.1093/intimm/dxab026 -
Matrix Biology : Journal of the... Nov 2018The composition and mechanical properties of the extracellular matrix are dramatically altered during the development and progression of pulmonary fibrosis. Recent... (Review)
Review
The composition and mechanical properties of the extracellular matrix are dramatically altered during the development and progression of pulmonary fibrosis. Recent evidence indicates that these changes in matrix composition and mechanics are not only end-results of fibrotic remodeling, but active participants in driving disease progression. These insights have stimulated interest in identifying the components and physical aspects of the matrix that contribute to cell activation and disease initiation and progression. This review summarizes current knowledge regarding the biomechanics and dynamics of the ECM in mouse models and human IPF, and discusses how matrix mechanical and compositional changes might be non-invasively assessed, therapeutically targeted, and biologically restored to resolve fibrosis.
Topics: Animals; Biomechanical Phenomena; Disease Models, Animal; Disease Progression; Extracellular Matrix; Extracellular Matrix Proteins; Humans; Mice; Pulmonary Fibrosis
PubMed: 29274939
DOI: 10.1016/j.matbio.2017.12.004 -
Apoptosis : An International Journal on... Dec 2023Pulmonary fibrosis (PF) is a disease in which excessive extracellular matrix (ECM) accumulation occurs in pulmonary mesenchyme, which induces the destruction of alveolar... (Review)
Review
Pulmonary fibrosis (PF) is a disease in which excessive extracellular matrix (ECM) accumulation occurs in pulmonary mesenchyme, which induces the destruction of alveolar structures and poor prognosis. Macrophage death is responsible for ECM accumulation after alveolar epithelial injury in PF. Depending on the local micro-environments, macrophages can be polarized to either classically activated (M1) or alternatively activated (M2) macrophage phenotypes. In general, M1 macrophages can promote inflammation and sterilization, stop the continuous damage process and prevent excessive repair, while M2 macrophages are anti-inflammatory and promote tissue repair, and excessive M2 macrophage activity may inhibit the absorption and degradation of ECM. Emerging evidence has revealed that death forms such as pyroptosis mediated by inflammasome affect polarization direction and ultimately lead to the development of PF. Pharmacological manipulation of macrophages death signals may serve as a logical therapeutic strategy for PF. This review will focus on the current state of knowledge regarding the regulation and underlying mechanisms of macrophages and their mediators in the influence of macrophage death on the development of PF. We expect to provide help in developing effective therapeutic strategies in clinical settings.
Topics: Humans; Macrophages, Alveolar; Pulmonary Fibrosis; Apoptosis; Macrophages; Inflammation
PubMed: 37707713
DOI: 10.1007/s10495-023-01888-4