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

Abstract

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.

The Modular µSiM: A Mass Produced, Rapidly Assembled, and Reconfigurable Platform for the Study of Barrier Tissue Models In Vitro

“…[66] The similar configuration might be used to study lung-blood barrier, where an interstitial space separates barriers created by the vascular endothelial cells and lung epithelial cells. [67,68] Our second example swapped our nanoporous membranes for dual-scale membranes to study immune cell migration. While quantification of migration in terms of percent migration in this study was challenging, due to the limited access of immune cells to the membrane window and low levels of spontaneous T cell migration, this will be addressed in future studies by incorporating the flow module, [30] which limits the immune cell access to just around the membrane window.…”

The Modular µSiM: a Mass Produced, Rapidly Assembled, and Reconfigurable Platform for the Study of Barrier Tissue ModelsIn Vitro

“…[64] The similar configuration might be used to study lung-blood barrier, where an interstitial space separates barriers created by the vascular endothelial cells and lung epithelial cells. [65][66] Our second example swapped our nanoporous membranes for dual-scale membranes to study immune cell migration. While quantification of migration in terms of percent migration in this study was challenging, due to the limited access of immune cells to the membrane window, this will be addressed in future studies by incorporating the flow module, [27] which limits the immune cell access to just around the membrane window.…”

Early prediction of bronchopulmonary dysplasia: can noninvasive monitoring methods be essential?

“…Genomic analysis may help in the future by identifying newborns with a greater risk of this condition so that they may get personalized therapy [142]. Furthermore, epigenetic processes may regulate genetic expression by either activating or silencing the genetic material encoded by the genome [143]. Fujioka et al [144] obtained genomic DNA from 97 VLBWIs' umbilical cords, UCB, or buccal mucosa.…”