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REVIEW ARTICLE

More than a Genetic Code: Epigenetics of Lung Fibrosis Krystian Bartczak1   · Adam J. Białas2 · Mateusz J. Kotecki1 · Paweł Górski1 · Wojciech J. Piotrowski1

© The Author(s) 2020

Abstract At the end of the last century, genetic studies reported that genetic information is not transmitted solely by DNA, but is also transmitted by other mechanisms, named as epigenetics. The well-described epigenetic mechanisms include DNA methylation, biochemical modifications of histones, and microRNAs. The role of altered epigenetics in the biology of various fibrotic diseases is well-established, and recent advances demonstrate its importance in the pathogenesis of pulmonary fibrosis— predominantly referring to idiopathic pulmonary fibrosis, the most lethal of the interstitial lung diseases. The deficiency in effective medications suggests an urgent need to better understand the underlying pathobiology. This review summarizes the current knowledge concerning epigenetic changes in pulmonary fibrosis and associations of these changes with several cellular pathways of known significance in its pathogenesis. It also designates the most promising substances for further research that may bring us closer to new therapeutic options.

Key Points  Epigenetic information is crucial for appropriate proliferation, maturation, and functioning of pulmonary fibroblasts and epithelial cells. Lung tissue affected by fibrosis presents numerous alterations in epigenetic code, many of them associated with regions that code proteins of known contribution to the pathogenesis of fibrosis. Specific agents that can modify the epigenome arise as potential medications for pulmonary fibrosis.

1 Introduction Interstitial lung diseases (ILDs) are a group of entities that predominantly affect lung interstitium. These diseases correspond to at least 15% of all known respiratory diseases. * Krystian Bartczak [email protected] 1



Department of Pneumology and Allergology, The Medical University of Lodz, Kopcińskiego 22, 90‑153 Lodz, Poland



Department of Pathobiology of Respiratory Diseases, The Medical University of Lodz, Lodz, Poland

2

These are classified into subgroups, including idiopathic interstitial pneumonias (e.g., idiopathic pulmonary fibrosis [IPF]) and ILD with granuloma formation (e.g., sarcoidosis). Importantly, some ILDs can be induced by drugs or occupational factors (asbestos, beryllium, etc.), while others are associated with connective tissue disease (CTD)— mainly rheumatoid arthritis, scleroderma, polymyositis, or dermatomyositis. The diagnosis and management of these diseases rely on clinical, radiological, and histopathological findings. The patient’s smoking status, exposure to toxins, coexistent diseases, and drug history should be noted carefully during an examination. The vast majority of symptoms of ILDs are limited to the respiratory tract (these would include dyspnea, cough, and less frequently wheezing and hemoptysis), but extrapulmonary symptoms may be present, and in many cases they are as