More than a Genetic Code: Epigenetics of Lung Fibrosis

Bartczak, Krystian; Białas, Adam J.; Kotecki, Mateusz; Górski, Paweł; Piotrowski, Wojciech J.

doi:10.1007/s40291-020-00490-7

Cited by 23 publications

(18 citation statements)

References 141 publications

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“…), the level of surfactant protein C (Sp-C), the activation and proliferation of fibroblasts are all significantly affected. Additionally, histone modifications can also affect the anti-apoptotic ability of fibroblasts by inhibiting anti-fibrotic genes such as FAS and caveolin 1 (Cav-1) ( Bartczak et al, 2020 ). Ligresti,G et al identified that histone methyltransferase G9a/chromobox homolog 5 (CBX5)/methylated lysine 9 residue on histone 3 (H3K9me) were key regulators of fibroblast activation, and determined that by participating in the CBX5/G9a pathway, TGFβ and increased matrix stiffness effectively inhibited PGC1α expression in lung fibroblasts ( Ligresti et al, 2019 ).…”

Section: Risk Factorsmentioning

confidence: 99%

Idiopathic Pulmonary Fibrosis: An Update on Pathogenesis

et al. 2022

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Idiopathic pulmonary fibrosis (IPF) is a progressive, lethal fibrotic lung disease that occurs primarily in middle-aged and elderly adults. It is a major cause of morbidity and mortality. With an increase in life expectancy, the economic burden of IPF is expected to continuously rise in the near future. Although the exact pathophysiological mechanisms underlying IPF remain not known. Significant progress has been made in our understanding of the pathogenesis of this devastating disease in last decade. The current paradigm assumes that IPF results from sustained or repetitive lung epithelial injury and subsequent activation of fibroblasts and myofibroblast differentiation. Persistent myofibroblast phenotype contributes to excessive deposition of the extracellular matrix (ECM) and aberrant lung repair, leading to tissue scar formation, distortion of the alveolar structure, and irreversible loss of lung function. Treatments of patients with IPF by pirfenidone and nintedanib have shown significant reduction of lung function decline and slowing of disease progression in patients with IPF. However, these drugs do not cure the disease. In this review, we discuss recent advances on the pathogenesis of IPF and highlight the development of novel therapeutic strategies against the disease.

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Section: Risk Factorsmentioning

confidence: 99%

Idiopathic Pulmonary Fibrosis: An Update on Pathogenesis

et al. 2022

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“…Pulmonary fibrosis (PF) includes more than 200 different pathological conditions characterized by inflammation and scar tissue formation in the lungs. PF can be grouped in five categories: drug-induced, radiation-induced, environmental, autoimmune, and occupational ( 1 ). However, the most common type of PF is represented by the “Idiopathic Pulmonary Fibrosis” (IPF), whose etiology remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Endogenous Long Pentraxin 3 Exerts a Protective Role in a Murine Model of Pulmonary Fibrosis

et al. 2021

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Pulmonary fibrosis is a progressive scarring disease of the lungs, characterized by inflammation, fibroblast activation, and deposition of extracellular matrix. The long pentraxin 3 (PTX3) is a member of the pentraxin family with non-redundant functions in innate immune responses, tissue repair, and haemostasis. The role played in the lungs by PTX3 during the fibrotic process has not been elucidated. In this study, the impact of PTX3 expression on lung fibrosis was assessed in an intratracheal bleomycin (BLM)-induced murine model of the disease applied to wild type animals, transgenic mice characterized by endothelial overexpression and stromal accumulation of PTX3 (Tie2-PTX3 mice), and genetically deficient Ptx3−/− animals. Our data demonstrate that PTX3 is produced during BLM-induced fibrosis in wild type mice, and that PTX3 accumulation in the stroma compartment of Tie2-PTX3 mice limits the formation of fibrotic tissue in the lungs, with reduced fibroblast activation and collagen deposition, and a decrease in the recruitment of the immune infiltrate. Conversely, Ptx3-null mice showed an exacerbated fibrotic response and decreased survival in response to BLM treatment. These results underline the protective role of endogenous PTX3 during lung fibrosis and pave the way for the study of novel PTX3-derived therapeutic approaches to the disease.

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“…Moreover, miRNAs have been associated with almost every stage in the pathogenesis of IPF including lung epithelial repair; epithelial–mesenchymal transition (EMT) such as let-7d, miR-200, miR-26a, and miR-375; activation of fibroblast and their trans differentiation to myofibroblasts such as miR-21, miR-155, miR-26a, miR-27a-3p, miR-9-5p; AECII cell senescence; and regulation of collagen production such as miR-320a [ 116 , 117 , 118 ]. MicroRNAs are both upregulated and downregulated during the pathogenesis of IPF and were shown to have both pro-fibrotic and anti-fibrotic roles in the pathogenesis of the disease [ 119 ]. Interestingly a study identified 47 significantly differentially expressed serum miRNAs from IPF patients compared with healthy controls including 21 upregulated miRNAs and 26 downregulated miRNAs [ 120 ].…”

Section: Epigenetic Dysregulation In Ipf and Copdmentioning

confidence: 99%

Epigenetic Mechanisms in Parenchymal Lung Diseases: Bystanders or Therapeutic Targets?

Avci

Sarvari

Savai

et al. 2022

IJMS

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Epigenetic responses due to environmental changes alter chromatin structure, which in turn modifies the phenotype, gene expression profile, and activity of each cell type that has a role in the pathophysiology of a disease. Pulmonary diseases are one of the major causes of death in the world, including lung cancer, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), lung tuberculosis, pulmonary embolism, and asthma. Several lines of evidence indicate that epigenetic modifications may be one of the main factors to explain the increasing incidence and prevalence of lung diseases including IPF and COPD. Interestingly, isolated fibroblasts and smooth muscle cells from patients with pulmonary diseases such as IPF and PH that were cultured ex vivo maintained the disease phenotype. The cells often show a hyper-proliferative, apoptosis-resistant phenotype with increased expression of extracellular matrix (ECM) and activated focal adhesions suggesting the presence of an epigenetically imprinted phenotype. Moreover, many abnormalities observed in molecular processes in IPF patients are shown to be epigenetically regulated, such as innate immunity, cellular senescence, and apoptotic cell death. DNA methylation, histone modification, and microRNA regulation constitute the most common epigenetic modification mechanisms.

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More than a Genetic Code: Epigenetics of Lung Fibrosis

Cited by 23 publications

References 141 publications

Idiopathic Pulmonary Fibrosis: An Update on Pathogenesis

Idiopathic Pulmonary Fibrosis: An Update on Pathogenesis

Endogenous Long Pentraxin 3 Exerts a Protective Role in a Murine Model of Pulmonary Fibrosis

Epigenetic Mechanisms in Parenchymal Lung Diseases: Bystanders or Therapeutic Targets?

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