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Nursing Standard (Royal College of... Sep 2014
Topics: Education, Nursing, Continuing; Humans; Idiopathic Pulmonary Fibrosis; Prognosis; United Kingdom
PubMed: 25159953
DOI: 10.7748/ns.28.52.19.s21 -
Redox Biology Oct 2016Redox signaling and oxidative stress are associated with tissue fibrosis and aging. Aging is recognized as a major risk factor for fibrotic diseases involving multiple... (Review)
Review
Redox signaling and oxidative stress are associated with tissue fibrosis and aging. Aging is recognized as a major risk factor for fibrotic diseases involving multiple organ systems, including that of the lung. A number of oxidant generating enzymes are upregulated while antioxidant defenses are deficient with aging and cellular senescence, leading to redox imbalance and oxidative stress. However, the precise mechanisms by which redox signaling and oxidative stress contribute to the pathogenesis of lung fibrosis are not well understood. Tissue repair is a highly regulated process that involves the interactions of several cell types, including epithelial cells, fibroblasts and inflammatory cells. Fibrosis may develop when these interactions are dysregulated with the acquisition of pro-fibrotic cellular phenotypes. In this review, we explore the roles of redox mechanisms that promote and perpetuate fibrosis in the context of cellular senescence and aging.
Topics: Age Factors; Aging; Animals; Apoptosis; Cellular Senescence; Epithelial Cells; Epithelial-Mesenchymal Transition; Fibroblasts; Humans; Molecular Targeted Therapy; Oxidation-Reduction; Oxidative Stress; Phenotype; Pulmonary Fibrosis; Reactive Oxygen Species
PubMed: 27394680
DOI: 10.1016/j.redox.2016.06.005 -
The Yale Journal of Biology and Medicine Jun 2017Pulmonary fibrosis is a form of lung disease that develops due to aberrant wound-healing following repeated alveoli injury in genetically susceptible individuals,... (Review)
Review
Pulmonary fibrosis is a form of lung disease that develops due to aberrant wound-healing following repeated alveoli injury in genetically susceptible individuals, resulting in chronic inflammation, excess deposition of the extracellular matrix components, mainly collagen, and scarring of lung tissue. In addition to irradiation, environmental agents such occupational inhalants, and chemotherapeutic agents, microbial agents also play a role in the etiology of the disease. While viruses have received the most attention, emerging evidence suggest that bacteria and fungi also play a part in the etiology of pulmonary fibrosis. Furthermore, successful use of antibiotics, antiviral and antifungal drugs in several studies to attenuate fibrosis progression is also an indication of microbial involvement in the pathogenesis of the disease and could be a promising therapeutic modality for treating pulmonary fibrosis initiated or exacerbated by infectious agents.
Topics: Animals; Anti-Infective Agents; Bacterial Infections; Disease Models, Animal; Humans; Mice; Mycoses; Pulmonary Fibrosis; Vaccination; Virus Diseases
PubMed: 28656009
DOI: No ID Found -
American Journal of Respiratory and... Aug 2019
Review
Topics: Humans; Idiopathic Pulmonary Fibrosis
PubMed: 31022351
DOI: 10.1164/rccm.201903-0542UP -
Matrix Metalloproteinases and Their Inhibitors in Pulmonary Fibrosis: EMMPRIN/CD147 Comes into Play.International Journal of Molecular... Jun 2022Pulmonary fibrosis (PF) is characterized by aberrant extracellular matrix (ECM) deposition, activation of fibroblasts to myofibroblasts and parenchymal disorganization,... (Review)
Review
Pulmonary fibrosis (PF) is characterized by aberrant extracellular matrix (ECM) deposition, activation of fibroblasts to myofibroblasts and parenchymal disorganization, which have an impact on the biomechanical traits of the lung. In this context, the balance between matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) is lost. Interestingly, several MMPs are overexpressed during PF and exhibit a clear profibrotic role (MMP-2, -3, -8, -11, -12 and -28), but a few are antifibrotic (MMP-19), have both profibrotic and antifibrotic capacity (MMP7), or execute an unclear (MMP-1, -9, -10, -13, -14) or unknown function. TIMPs are also overexpressed in PF; hence, the modulation and function of MMPs and TIMP are more complex than expected. EMMPRIN/CD147 (also known as basigin) is a transmembrane glycoprotein from the immunoglobulin superfamily (IgSF) that was first described to induce MMP activity in fibroblasts. It also interacts with other molecules to execute non-related MMP aactions well-described in cancer progression, migration, and invasion. Emerging evidence strongly suggests that CD147 plays a key role in PF not only by MMP induction but also by stimulating fibroblast myofibroblast transition. In this review, we study the structure and function of MMPs, TIMPs and CD147 in PF and their complex crosstalk between them.
Topics: Basigin; Extracellular Matrix; Humans; Matrix Metalloproteinases; Pulmonary Fibrosis; Tissue Inhibitor of Metalloproteinases
PubMed: 35805895
DOI: 10.3390/ijms23136894 -
Molecular Aspects of Medicine Dec 2017Inflammation and its timely resolution play a critical role in effective host defence and wound healing. Unresolved inflammatory responses underlie the pathology of many... (Review)
Review
Inflammation and its timely resolution play a critical role in effective host defence and wound healing. Unresolved inflammatory responses underlie the pathology of many prevalent diseases resulting in tissue fibrosis and eventual organ failure as typified by kidney, lung and liver fibrosis. The role of autocrine and paracrine mediators including cytokines, prostaglandins and leukotrienes in initiating and sustaining inflammation is well established. More recently a physiological role for specialized pro-resolving lipid mediators [SPMs] in modulating inflammatory responses and promoting the resolution of inflammation has been appreciated. As will be discussed in this review, SPMs not only attenuate the development of fibrosis through promoting the resolution of inflammation but may also directly suppress fibrotic responses. These findings suggest novel therapeutic paradigms to treat intractable life-limiting diseases such as renal fibrosis.
Topics: Animals; Biomarkers; Disease Progression; Fibrosis; Gene Expression Regulation; Humans; Inflammation Mediators; Kidney Diseases; Lipid Metabolism; Liver Cirrhosis; Pulmonary Fibrosis; Signal Transduction
PubMed: 28479307
DOI: 10.1016/j.mam.2017.05.001 -
Immunopharmacology and Immunotoxicology Apr 2020Paraquat (PQ) poisoning can induce mitophagy and pulmonary fibrosis. Cyclosporine A (CsA) is an inhibitor of mitophagy. This study aimed at investigating whether CsA...
Paraquat (PQ) poisoning can induce mitophagy and pulmonary fibrosis. Cyclosporine A (CsA) is an inhibitor of mitophagy. This study aimed at investigating whether CsA could inhibit PQ-induced mitophagy and pulmonary fibrosis in rats. Male Sprague-Dawley (SD) rats were treated with vehicle saline (control), 50 mg/kg PQ by gavage alone, or together with different doses of CsA. At 14 days post-induction, the levels of pulmonary fibrosis and PTEN-induced putative kinase 1 (PINK1) and Parkin expression in individual rats and mitochondrial membrane potential (MMP) in lung cells were measured. Moreover, A549 cells were treated with PQ or PQ + CsA for 24 h and the levels of PINK1, Parkin, fibronectin, collagen I and LC3 I and II expression and MMP were examined. Finally, the impact of PINK1 overexpression on the PQ or PQ + CsA-modulated fibronectin and collagen I expression in A549 cells was tested. PQ exposure significantly increased the levels of hydroxyproline and collagen I expression and collagen fiber accumulation in the lung of rats, which were mitigated by CsA treatment. Furthermore, treatment with CsA significantly improved the PQ-decreased MMP and abrogated PQ-upregulated PINK1 and Parkin expression in the lungs of rats. In addition, CsA treatment decreased the PQ-induced fibrosis and mitophagy and PQ-impaired MMP as well as PQ-upregulated PINK1 and Parkin expression in A549 cells. The later effect of CsA was abrogated by PINK1 overexpression in A549 cells. Therefore, CsA can inhibit the PQ-induced mitophagy and pulmonary fibrosis by attenuating the PINK1/Parkin signaling.
Topics: A549 Cells; Animals; Cyclosporine; Disease Models, Animal; Humans; Hydroxyproline; Lung; Male; Membrane Potential, Mitochondrial; Mitophagy; Paraquat; Protein Kinases; Pulmonary Fibrosis; Rats, Sprague-Dawley; Ubiquitin-Protein Ligases
PubMed: 32116062
DOI: 10.1080/08923973.2020.1729176 -
Clinical Medicine (London, England) Dec 2014Idiopathic pulmonary fibrosis (IPF) is a devastating condition with a poor prognosis and few treatment options. However, recent research into this condition has led to... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a devastating condition with a poor prognosis and few treatment options. However, recent research into this condition has led to considerable insights into the pathophysiology of the disease, resulting in the identification of potential biomarkers to aid diagnosis and stratification of patients and the development of novel therapies. In this review we will discuss the recent developments in this field and review how this knowledge has been translated into clinical trials and a paradigm shift in our approach to patients with IPF.
Topics: Biomarkers; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Pyridones
PubMed: 25468919
DOI: 10.7861/clinmedicine.14-6-s45 -
Methods in Molecular Biology (Clifton,... 2021The drug discovery pipeline, from discovery of therapeutic targets through preclinical and clinical development phases, to an approved product by health authorities, is...
The drug discovery pipeline, from discovery of therapeutic targets through preclinical and clinical development phases, to an approved product by health authorities, is a time-consuming and costly process, where a lead candidates' success at reaching the final stage is rare. Although the time from discovery to final approval has been reduced over the last decade, there is still potential to further optimize and streamline the evaluation process of each candidate as it moves through the different development phases. In this book chapter, we describe our preclinical strategies and overall decision-making process designed to evaluate the tolerability and efficacy of therapeutic candidates suitable for patients diagnosed with fibrotic lung disease. We also describe the benefits of conducting preliminary discovery trials, to aid in the selection of suitable primary and secondary outcomes to be further evaluated and assessed in subsequent internal and external validation studies. We outline all relevant research methodologies and protocols routinely performed by our research group and hope that these strategies and protocols will be a useful guide for biomedical and translational researchers aiming to develop safe and beneficial therapies for patients with fibrotic lung disease.
Topics: Animals; Bleomycin; Computational Biology; Decision Making; Disease Models, Animal; Drug Evaluation, Preclinical; Gene Expression Regulation; Gene Regulatory Networks; Humans; Mice; Mice, Inbred C57BL; Pulmonary Fibrosis
PubMed: 34028751
DOI: 10.1007/978-1-0716-1382-5_21 -
Expert Review of Respiratory Medicine Jun 2020: Idiopathic pulmonary fibrosis (IPF) is a chronic, devastating, and progressive lung disease that is characterized by fibrosis and respiratory failure. IPF holds high... (Review)
Review
: Idiopathic pulmonary fibrosis (IPF) is a chronic, devastating, and progressive lung disease that is characterized by fibrosis and respiratory failure. IPF holds high morbidity and poor prognosis and still faces considerable problems of reliable diagnosis and valid prognosis. A growing body of literature have reported changes in the level of various biomarkers in IPF patients, which means that they are expected to become a new tool for the clinical practice of IPF.: We reviewed the recent literature about biomarkers and focus on the role they play in IPF. We systematically searched Medline/PubMed through February 2020. Many works of literature have shown that a variety of biomolecules and genomics played multiple roles in the diagnosis or differential diagnosis, prognosis, and indication of acute deterioration of IPF and so on.: Significant advances have been made in the role of biomarkers for IPF these years; however, current data indicate that a single biomarker is unlikely to have a transformative effect on clinical practice; therefore, the combined effect of various biomarkers can be considered to improve the accuracy of diagnosis and prognosis. Further research of biomarkers may provide new insights for the diagnosis, prognosis, and even therapy of IPF.
Topics: Biomarkers; Diagnosis, Differential; Humans; Idiopathic Pulmonary Fibrosis; Lung; Prognosis
PubMed: 32187497
DOI: 10.1080/17476348.2020.1745066