Chronic obstructive pulmonary disease (COPD) is characterised by persistent inflammation, progressive airway narrowing, and alveoli destruction. The cause of these symptoms is believed to be that the function of specific lung cells, the lung fibroblasts, is disturbed. DZL scientist Dr. Maria Llamazares-Prada and German and British scientists have identified chemical changes in the genetic material of the fibroblasts of COPD patients and, thus, new targets for treating COPD. These are so-called epigenetic changes that influence whether a gene is active.
“For example, we know that smoking - the main risk factor for COPD – strongly modifies the epigenome of lung cells. However, we do not yet know which epigenetic changes occur specifically in lung fibroblasts during the course of the disease and how these changes trigger aberrant signaling pathways that drive the impaired functions of fibroblasts in COPD," says Llamazares-Prada.
Together with their colleagues, Uwe Schwartz from the University of Regensburg and Llamazares-Prada have now, for the first time, analysed the DNA methylation pattern of COPD fibroblasts' DNA at different stages of the disease. The attachment of methyl groups to DNA is the best-studied epigenetic mechanism.
Changes occur at an early stage of the disease
The researchers found that significant changes in the methylation pattern occur early in the disease. And in particular in areas of the genome through which proteins influence the activity of various genes.
Renata Z. Jurkowska, the study's lead author, explains: "Our aim was to support the development of new diagnostic strategies for early COPD and the rational selection of targets with potential disease-modifying activities. Further research is needed to pinpoint the target genes of the identified regulators in lung fibroblasts and their specific role in disease development."
Original publication: Schwartz U, Llamazares Prada M, Pohl ST, et al. High-resolution transcriptomic and epigenetic profiling identifies novel regulators of COPD [published online ahead of print, 2023 May 5]. EMBO J. 2023;e111272. doi: 10.15252/embj.2022111272