What is it about?

Chronic Obstructive Pulmonary Disease (COPD) is a debilitating pulmonary disease. The current treatment is palliative because the mechanisms and druggable targets are not known. The role of a nuclear chromatin modification enzyme, histone deacetylase HDAC2 in DNA damage response and cellular senescence by cigarette smoke leading to COPD/emphysema is not known. Here, we provide data on HDAC2-p16 mediated regulation of epithelial cell senescence in COPD/emphysema, increased DNA damage response, senescence-associated secretory phenotype (SASP), and lymphoid follicle formation which are regulated by HDAC2. It is possible that senesced lung epithelial cells in COPD which has reduced HDAC2 may contribute to lymphoid follicle formation and steroid resistance which are seen in lungs of patients with COPD in advanced stages. This information will move the field forward in understanding the pathogenesis of COPD and lung aging per se.

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Why is it important?

This research is highly relevant for both basic science and specialized scientists working on organ aging and pulmonary diseases. Future studies are needed where the targeted drugs/senolytic agents can be tested to augment HDAC2 activity/levels and/or inhibits cellular senescence, thereby providing protection against cigarette smoke-induced COPD/emphysema, lymphoid follicle formation, and steroid resistance.

Perspectives

The mechanisms of lung aging and decline in host-defense immunity in the pathogenesis of COPD are not known. Here, we provide some mechanistic insights in lung cellular senescence, inflammation, and lymphoid follicle formation by a nuclear deacetylase, HDAC2. This may be associated with steroid resistance in advanced stages of COPD progression and harboring infections in the lungs. Targeted senolytic agents/drugs can be tested for treatment of advanced stages of COPD/emphysema.

Irfan Rahman
University of Rochester

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This page is a summary of: Genetic ablation of histone deacetylase 2 leads to lung cellular senescence and lymphoid follicle formation in COPD/emphysema, The FASEB Journal, September 2018, Federation of American Societies For Experimental Biology (FASEB),
DOI: 10.1096/fj.201701518r.
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