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Respirology (Carlton, Vic.) Apr 2021
Topics: Air Pollution; Humans; Idiopathic Pulmonary Fibrosis
PubMed: 33398912
DOI: 10.1111/resp.14004 -
Clinics in Chest Medicine Jun 2021Idiopathic pulmonary fibrosis (IPF) is a devastating disease for patients and their loved ones. Since initial efforts to characterize this disease in the 1960s,... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a devastating disease for patients and their loved ones. Since initial efforts to characterize this disease in the 1960s, understanding of IPF has evolved considerably. Such evolution has continually challenged prior diagnostic and treatment paradigms, ushering in an era of higher confidence diagnoses with less invasive procedures and more effective treatments. This review details how research and clinical experience over the past half century have led to a rethinking of IPF. Here, the evolution in understanding of IPF pathogenesis, diagnostic evaluation and treatment approach is discussed.
Topics: Humans; Idiopathic Pulmonary Fibrosis
PubMed: 34024402
DOI: 10.1016/j.ccm.2021.03.005 -
Nature Communications Dec 2023Pulmonary fibrosis (PF), a condition characterized by inflammation and collagen deposition in the alveolar interstitium, causes dyspnea and fatal outcomes. Although the...
Pulmonary fibrosis (PF), a condition characterized by inflammation and collagen deposition in the alveolar interstitium, causes dyspnea and fatal outcomes. Although the bleomycin-induced PF mouse model has improved our understanding of exogenous factor-induced fibrosis, the mechanism governing endogenous factor-induced fibrosis remains unknown. Here, we find that Ifngr1Rag2 mice, which lack the critical suppression factor for group 2 innate lymphoid cells (ILC2), develop PF spontaneously. The onset phase of fibrosis includes ILC2 subpopulations with a high Il1rl1 (IL-33 receptor) expression, and fibrosis does not develop in ILC-deficient or IL-33-deficient mice. Although ILC2s are normally localized near bronchioles and blood vessels, ILC2s are increased in fibrotic areas along with IL-33 positive fibroblasts during fibrosis. Co-culture analysis shows that activated-ILC2s directly induce collagen production from fibroblasts. Furthermore, increased IL1RL1 and decreased IFNGR1 expressions are confirmed in ILC2s from individuals with idiopathic PF, highlighting the applicability of Ifngr1Rag2 mice as a mouse model for fibrosis research.
Topics: Animals; Mice; Pulmonary Fibrosis; Immunity, Innate; Interleukin-33; Lymphocytes; Fibrosis; Collagen; Lung; Mice, Inbred C57BL; Interleukin-1 Receptor-Like 1 Protein
PubMed: 38097562
DOI: 10.1038/s41467-023-43336-6 -
European Respiratory Review : An... Sep 2023Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. A minority of patients with sarcoidosis develop sarcoidosis-associated pulmonary fibrosis... (Review)
Review
Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. A minority of patients with sarcoidosis develop sarcoidosis-associated pulmonary fibrosis (SAPF), which may become progressive. Genetic profiles differ between patients with progressive and self-limiting disease. The mechanisms of fibrosis in SAPF are not fully understood, but SAPF is likely a distinct clinicopathological entity, rather than a continuum of acute inflammatory sarcoidosis. Risk factors for the development of SAPF have been identified; however, at present, it is not possible to make a robust prediction of risk for an individual patient. The bulk of fibrotic abnormalities in SAPF are located in the upper and middle zones of the lungs. A greater extent of SAPF on imaging is associated with a worse prognosis. Patients with SAPF are typically treated with corticosteroids, second-line agents such as methotrexate or azathioprine, or third-line agents such as tumour necrosis factor inhibitors. The antifibrotic drug nintedanib is an approved treatment for slowing the decline in lung function in patients with progressive fibrosing interstitial lung diseases, but more evidence is needed to assess its efficacy in SAPF. The management of patients with SAPF should include the identification and treatment of complications such as bronchiectasis and pulmonary hypertension. Further research is needed into the mechanisms underlying SAPF and biomarkers that predict its clinical course.
Topics: Humans; Pulmonary Fibrosis; Lung; Lung Diseases, Interstitial; Sarcoidosis; Risk Factors; Disease Progression
PubMed: 37758275
DOI: 10.1183/16000617.0085-2023 -
Respirology (Carlton, Vic.) Mar 2022
Topics: Alveolitis, Extrinsic Allergic; Humans; Pulmonary Fibrosis
PubMed: 35146840
DOI: 10.1111/resp.14225 -
QJM : Monthly Journal of the... Nov 2021
Topics: COVID-19; Humans; Lung; Pulmonary Fibrosis; SARS-CoV-2
PubMed: 34002238
DOI: 10.1093/qjmed/hcab121 -
Medecine Sciences : M/S 2022Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal lung disease of unknown origin. It is characterized by aberrant scarring of the alveolar... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal lung disease of unknown origin. It is characterized by aberrant scarring of the alveolar epithelium leading to an accumulation of extracellular matrix (ECM). Fibroblastic foci, consisting of fibroblasts and myofibroblasts, are responsible for the excessive production of ECM. The two therapeutic molecules available on the market to date only allow to slow down the evolution of the disease. In this review, we present the mechanisms involved in the progression of the disease, its treatments and the study models.
Topics: Extracellular Matrix; Fibroblasts; Humans; Idiopathic Pulmonary Fibrosis; Lung; Myofibroblasts
PubMed: 35766856
DOI: 10.1051/medsci/2022084 -
Archivos de Bronconeumologia Apr 2022
Topics: COVID-19; Humans; Lung; Pulmonary Fibrosis; Tomography, X-Ray Computed
PubMed: 35491285
DOI: 10.1016/j.arbres.2022.03.007 -
Cellular & Molecular Biology Letters Dec 2023Pulmonary fibrosis is a growing clinical problem that develops as a result of abnormal wound healing, leading to breathlessness, pulmonary dysfunction and ultimately...
BACKGROUND
Pulmonary fibrosis is a growing clinical problem that develops as a result of abnormal wound healing, leading to breathlessness, pulmonary dysfunction and ultimately death. However, therapeutic options for pulmonary fibrosis are limited because the underlying pathogenesis remains incompletely understood. Circular RNAs, as key regulators in various diseases, remain poorly understood in pulmonary fibrosis induced by silica.
METHODS
We performed studies with fibroblast cell lines and silica-induced mouse pulmonary fibrosis models. The expression of circZNF609, miR-145-5p, and KLF4 was determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. RNA immunoprecipitation (RIP) assays and m6A RNA immunoprecipitation assays (MeRIP), Western blotting, immunofluorescence assays, and CCK8 were performed to investigate the role of the circZNF609/miR-145-5p/KLF4 axis and circZNF609-encoded peptides in fibroblast activation.
RESULTS
Our data showed that circZNF609 was downregulated in activated fibroblasts and silica-induced fibrotic mouse lung tissues. Overexpression of circZNF609 could inhibit fibroblast activation induced by transforming growth factor-β1 (TGF-β1). Mechanically, we revealed that circZNF609 regulates pulmonary fibrosis via miR-145-5p/KLF4 axis and circZNF609-encoded peptides. Furthermore, circZNF609 was highly methylated and its expression was controlled by N6-methyladenosine (m6A) modification. Lastly, in vivo studies revealed that overexpression of circZNF609 attenuates silica-induced lung fibrosis in mice.
CONCLUSIONS
Our data indicate that circZNF609 is a critical regulator of fibroblast activation and silica-induced lung fibrosis. The circZNF609 and its derived peptides may represent novel promising targets for the treatment of pulmonary fibrosis.
Topics: Animals; Mice; Lung; MicroRNAs; Pulmonary Fibrosis; Silicon Dioxide; Transforming Growth Factor beta1; Kruppel-Like Factor 4; RNA, Circular
PubMed: 38105235
DOI: 10.1186/s11658-023-00518-w -
Frontiers in Immunology 2023Post-acute COVID-19 sequelae, commonly known as long COVID, encompasses a range of systemic symptoms experienced by a significant number of COVID-19 survivors. The... (Review)
Review
Post-acute COVID-19 sequelae, commonly known as long COVID, encompasses a range of systemic symptoms experienced by a significant number of COVID-19 survivors. The underlying pathophysiology of long COVID has become a topic of intense research discussion. While chronic inflammation in long COVID has received considerable attention, the role of neutrophils, which are the most abundant of all immune cells and primary responders to inflammation, has been unfortunately overlooked, perhaps due to their short lifespan. In this review, we discuss the emerging role of neutrophil extracellular traps (NETs) in the persistent inflammatory response observed in long COVID patients. We present early evidence linking the persistence of NETs to pulmonary fibrosis, cardiovascular abnormalities, and neurological dysfunction in long COVID. Several uncertainties require investigation in future studies. These include the mechanisms by which SARS-CoV-2 brings about sustained neutrophil activation phenotypes after infection resolution; whether the heterogeneity of neutrophils seen in acute SARS-CoV-2 infection persists into the chronic phase; whether the presence of autoantibodies in long COVID can induce NETs and protect them from degradation; whether NETs exert differential, organ-specific effects; specifically which NET components contribute to organ-specific pathologies, such as pulmonary fibrosis; and whether senescent cells can drive NET formation through their pro-inflammatory secretome in long COVID. Answering these questions may pave the way for the development of clinically applicable strategies targeting NETs, providing relief for this emerging health crisis.
Topics: Humans; Extracellular Traps; COVID-19; Post-Acute COVID-19 Syndrome; SARS-CoV-2; Pulmonary Fibrosis; Inflammation
PubMed: 37828990
DOI: 10.3389/fimmu.2023.1254310