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Respiratory Medicine Nov 2006Idiopathic pulmonary fibrosis (IPF) is an important, and devastating, interstitial lung disease. It has a median mortality of only 3 years, worse than many cancers, and... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is an important, and devastating, interstitial lung disease. It has a median mortality of only 3 years, worse than many cancers, and its incidence continues to rise. In this article, an overview of key developments in our understanding and clinical management of IPF will be provided.
Topics: Administration, Oral; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Combined Modality Therapy; Cortisone; Humans; Prognosis; Pulmonary Fibrosis
PubMed: 16987645
DOI: 10.1016/j.rmed.2006.08.017 -
European Respiratory Review : An... Mar 2012Interstitial lung diseases (ILDs) are a group of heterogeneous disorders, either idiopathic or associated with injurious or inflammatory causes, in which the major site... (Review)
Review
Interstitial lung diseases (ILDs) are a group of heterogeneous disorders, either idiopathic or associated with injurious or inflammatory causes, in which the major site of damage is the lung interstitium. For a long time, knowledge regarding pathogenesis was trivial and there were difficulties in diagnosing and subsequently treating these diseases. During the past decade, however, there has been an impressive development in the field of ILDs. Idiopathic pulmonary fibrosis, the most common and fatal form of ILD, was initially believed to be due to an inflammatory response to unknown lung injury, whereas nowadays it is believed to be the result of multiple injuries at different sites of the lung followed by aberrant repair. The integration of clinical, radiological and histological data, namely a multidisciplinary team (MDT) approach, has provided grounds for a more accurate diagnosis of ILDs, and helped the identification of different entities and development of different therapeutic approaches. However, because of the complexity of ILDs, even this approach may fail to establish a confident diagnosis. How should the clinician behave in this case and what are the pitfalls of the MDT approach? In addition, since diagnosis is the major predictor of prognosis, are there any other tools available to predict prognosis?
Topics: Humans; Inflammation; Lung Diseases, Interstitial; Prognosis; Pulmonary Fibrosis
PubMed: 22379174
DOI: 10.1183/09059180.00007611 -
Experimental & Molecular Medicine May 2019Prior studies have reported the presence of lung fibrosis and enhanced airway hyperresponsiveness (AHR) in mice with high-fat-diet (HFD)-induced obesity. This study...
Prior studies have reported the presence of lung fibrosis and enhanced airway hyperresponsiveness (AHR) in mice with high-fat-diet (HFD)-induced obesity. This study evaluated the role of TGF-β1 in HFD-induced AHR and lung fibrosis in a murine model. We generated HFD-induced obesity mice and performed glucose and insulin tolerance tests. HFD mice with or without ovalbumin sensitization and challenge were also treated with an anti-TGF-β1 neutralizing antibody. AHR to methacholine, inflammatory cells in the bronchoalveolar lavage fluid (BALF), and histological features were evaluated. Insulin was intranasally administered to normal diet (ND) mice, and in vitro insulin stimulation of BEAS-2b cells was performed. HFD-induced obesity mice had increased insulin resistance, enhanced AHR, peribronchial and perivascular fibrosis, and increased numbers of macrophages in the BALF. However, they did not have meaningful eosinophilic or neutrophilic inflammation in the lungs compared with ND mice. The HFD enhanced TGF-β1 expression in the bronchial epithelium, but we found no differences in the expression of interleukin (IL)-4 or IL-5 in lung homogenates. Administration of the anti-TGF-β1 antibody attenuated HFD-induced AHR and lung fibrosis. It also attenuated goblet cell hyperplasia, but did not affect the AHR and inflammatory cell infiltration induced by OVA challenge. The intranasal administration of insulin enhanced TGF-β1 expression in the bronchial epithelium and lung fibrosis. Stimulating BEAS-2b cells with insulin also increased TGF-β1 production by 24 h. We concluded that HFD-induced obesity-associated insulin resistance enhances TGF-β1 expression in the bronchial epithelium, which may play an important role in the development of lung fibrosis and AHR in obesity.
Topics: Animals; Diet, High-Fat; Insulin Resistance; Lung; Male; Mice, Inbred C57BL; Pulmonary Fibrosis; Signal Transduction; Transforming Growth Factor beta1
PubMed: 31133649
DOI: 10.1038/s12276-019-0258-7 -
Journal of Cellular Physiology Mar 2017Cellular oxidative stress is implicated not only in lung injury but also in contributing to the development of pulmonary fibrosis. We demonstrate that a cell-permeable...
Cellular oxidative stress is implicated not only in lung injury but also in contributing to the development of pulmonary fibrosis. We demonstrate that a cell-permeable superoxide dismutase (SOD) mimetic and peroxynitrite scavenger, manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) significantly inhibited bleomycin-induced fibrogenic effects both in vitro and in vivo. Further investigation into the underlying mechanisms revealed that MnTBAP targets canonical Wnt and non-canonical Wnt/Ca2+ signaling pathways, both of which were upregulated by bleomycin treatment. The effect of MnTBAP on canonical Wnt signaling was significant in vivo but inconclusive in vitro and the non-canonical Wnt/Ca2+ signaling pathway was observed to be the predominant pathway regulated by MnTBAP in bleomycin-induced pulmonary fibrosis. Furthermore, we show that the inhibitory effects of MnTBAP involve regulation of VEGF which is upstream of the Wnt signaling pathway. Overall, the data show that the superoxide scavenger MnTBAP attenuates bleomycin-induced pulmonary fibrosis by targeting VEGF and Wnt signaling pathways. J. Cell. Physiol. 232: 506-516, 2017. © 2016 Wiley Periodicals, Inc.
Topics: Animals; Biomarkers; Bleomycin; Calcium Signaling; Cell Line; Humans; Metalloporphyrins; Mice, Inbred C57BL; Neovascularization, Physiologic; Pulmonary Fibrosis; Up-Regulation; Vascular Endothelial Growth Factor A; Wnt Signaling Pathway
PubMed: 27649046
DOI: 10.1002/jcp.25608 -
European Journal of Pharmaceutical... Apr 2023Pulmonary fibrosis (PF) is a chronic, irreversible lung disease that is typically fatal and characterized by an abnormal fibrotic response. As a result, vast areas of... (Review)
Review
Pulmonary fibrosis (PF) is a chronic, irreversible lung disease that is typically fatal and characterized by an abnormal fibrotic response. As a result, vast areas of the lungs are gradually affected, and gas exchange is impaired, making it one of the world's leading causes of death. This can be attributed to a lack of understanding of the onset and progression of the disease, as well as a poor understanding of the mechanism of adverse responses to various factors, such as exposure to allergens, nanomaterials, environmental pollutants, etc. So far, the most frequently used preclinical evaluation paradigm for PF is still animal testing. Nonetheless, there is an urgent need to understand the factors that induce PF and find novel therapeutic targets for PF in humans. In this regard, robust and realistic in vitro fibrosis models are required to understand the mechanism of adverse responses. Over the years, several in vitro and ex vivo models have been developed with the goal of mimicking the biological barriers of the lung as closely as possible. This review summarizes recent progress towards the development of experimental models suitable for predicting fibrotic responses, with an emphasis on cell culture methods, nanomaterials, and a comparison of results from studies using cells from various species.
Topics: Animals; Humans; Pulmonary Fibrosis; Lung; Nanostructures; Cell Culture Techniques
PubMed: 36652970
DOI: 10.1016/j.ejps.2023.106387 -
Respiratory Medicine 2021
Topics: Antifibrotic Agents; Humans; Indoles; Pulmonary Fibrosis; Sarcoidosis, Pulmonary; Vital Capacity
PubMed: 33798872
DOI: 10.1016/j.rmed.2021.106371 -
Oxidative Medicine and Cellular... 2022First, the purity of hAD-MSCs was determined by morphological observation and FCM, and the effects on the survival of paraquat-poisoned Sprague-Dawley rats were...
METHODS
First, the purity of hAD-MSCs was determined by morphological observation and FCM, and the effects on the survival of paraquat-poisoned Sprague-Dawley rats were observed. All rats were randomly divided into three groups, defined as the sham control group ( = 8), model group ( = 15), and hAD-MSC-transplanted group ( = 17). Pneumonocyte damage and inflammatory cell infiltration were investigated in the three groups of rats, untreated control, paraquat only, and paraquat+hAD-MSC transplanted, using H&E staining. Fibrosis was investigated in three groups of rats using Masson's trichrome staining and Sirius red staining. The profibrotic factor TGF-1, the composition of fibrotic collagen HYP, and the hAD-MSC-secreted immunosuppressive factor HLA-G5 in serum were investigated in the three groups of rats using ELISA. Furthermore, the distribution of hAD-MSCs was investigated in the three groups of rats using immunohistochemistry and hematoxylin staining.
RESULTS
The hAD-MSCs exhibited typical hallmarks of MSCs, improved the state of being and survival of paraquat-poisoned rats, reduced both lung injury and inflammation, and inhibited the progression of pulmonary fibrosis by decreasing the deposition of collagen and the secretion of both TGF-1 and HYP. The hAD-MSCs could survive in damaged lungs and secreted appropriate amounts of HLA-G5 into the serum.
CONCLUSION
The obtained results indicate that hAD-MSCs used to treat paraquat-induced lung injury may work through anti-inflammatory and immunosuppressive pathways and the downregulation of profibrotic elements. This study suggests that the transplantation of hAD-MSCs is a promising therapeutic approach for the treatment of paraquat-intoxicated patients.
Topics: Acute Lung Injury; Amnion; Animals; Humans; Paraquat; Pulmonary Fibrosis; Rats; Rats, Sprague-Dawley
PubMed: 35345827
DOI: 10.1155/2022/3932070 -
Respiratory Research May 2022Pulmonary fibrosis is a progressive and usually lethal pulmonary disease. Despite considerable research efforts, no effective therapeutic strategy for pulmonary fibrosis...
BACKGROUND
Pulmonary fibrosis is a progressive and usually lethal pulmonary disease. Despite considerable research efforts, no effective therapeutic strategy for pulmonary fibrosis has been developed. NecroX-5 has been reported to possess anti-inflammatory, anti-oxidative and anti-tumor activities. In the present study, we aimed to determine whether NecroX-5 exhibits antifibrotic property in bleomycin (BLM)-induced pulmonary fibrosis.
RESULTS
We found that pre-treatment with NecroX-5 alleviated inflammatory response, reduced oxidative stress, inhibited epithelial-mesenchymal transition (EMT), and ameliorated pulmonary fibrosis in vivo and in vitro. Our data further indicated that NecroX-5 substantially reduced activation of NLRP3 inflammasome and TGF-β1/Smad2/3 signaling in vivo and in vitro. Additionally, NLRP3 overexpression significantly reversed the protective effects of NecroX-5 in lung epithelial cells exposed to BLM.
CONCLUSIONS
Overall, our results demonstrate the potent antifibrotic properties of NecroX-5 and its therapeutic potential for pulmonary fibrosis.
Topics: Animals; Bleomycin; Epithelial-Mesenchymal Transition; Heterocyclic Compounds, 4 or More Rings; Mice; NLR Family, Pyrin Domain-Containing 3 Protein; Pulmonary Fibrosis; Sulfones; Transforming Growth Factor beta1
PubMed: 35596212
DOI: 10.1186/s12931-022-02044-3 -
Annals of the New York Academy of... Nov 2020Exposure to vesicants, including sulfur mustard and nitrogen mustard, causes damage to the epithelia of the respiratory tract and the lung. With time, this progresses to... (Review)
Review
Exposure to vesicants, including sulfur mustard and nitrogen mustard, causes damage to the epithelia of the respiratory tract and the lung. With time, this progresses to chronic disease, most notably, pulmonary fibrosis. The pathogenic process involves persistent inflammation and the release of cytotoxic oxidants, cytokines, chemokines, and profibrotic growth factors, which leads to the collapse of lung architecture, with fibrotic involution of the lung parenchyma. At present, there are no effective treatments available to combat this pathological process. Recently, much interest has focused on nutraceuticals, substances derived from plants, herbs, and fruits, that exert pleiotropic effects on inflammatory cells and parenchymal cells that may be useful in reducing fibrogenesis. Some promising results have been obtained with nutraceuticals in experimental animal models of inflammation-driven fibrosis. This review summarizes the current knowledge on the putative preventive/therapeutic efficacy of nutraceuticals in progressive pulmonary fibrosis, with a focus on their activity against inflammatory reactions and profibrotic cell differentiation.
Topics: Animals; Chemical Warfare Agents; Dietary Supplements; Disease Models, Animal; Humans; Irritants; Mechlorethamine; Mustard Gas; Pulmonary Fibrosis
PubMed: 32725637
DOI: 10.1111/nyas.14442 -
The Journal of Gene Medicine Mar 2021Pulmonary fibrosis is characterized by progressive and irreversible scarring in the lungs with poor prognosis and treatment. It is caused by various factors, including... (Review)
Review
Pulmonary fibrosis is characterized by progressive and irreversible scarring in the lungs with poor prognosis and treatment. It is caused by various factors, including environmental and occupational exposures, and some rheumatic immune diseases. Even the rapid global spread of the COVID-19 pandemic can also cause pulmonary fibrosis with a high probability. Functions attributed to long non-coding RNAs (lncRNAs) make them highly attractive diagnostic and therapeutic targets in fibroproliferative diseases. Therefore, an understanding of the specific mechanisms by which lncRNAs regulate pulmonary fibrotic pathogenesis is urgently needed to identify new possibilities for therapy. In this review, we focus on the molecular mechanisms and implications of lncRNAs targeted protein-coding and non-coding genes during pulmonary fibrogenesis, and systematically analyze the communication of lncRNAs with various types of RNAs, including microRNA, circular RNA and mRNA. Finally, we propose the potential approach of lncRNA-based diagnosis and therapy for pulmonary fibrosis. We hope that understanding these interactions between protein-coding and non-coding genes will contribute to the development of lncRNA-based clinical applications for pulmonary fibrosis.
Topics: Gene Expression Regulation; Genetic Markers; Genetic Therapy; Humans; MicroRNAs; Proteins; Pulmonary Fibrosis; RNA, Circular; RNA, Long Noncoding
PubMed: 33533071
DOI: 10.1002/jgm.3318