AUTHOR=Dong Yan , Cao Hongbao , Cao Rongyuan , Baranova Ancha 

TITLE=TNFRSF12A and CD38 Contribute to a Vicious Circle for Chronic Obstructive Pulmonary Disease by Engaging Senescence Pathways

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.00330

DOI=10.3389/fcell.2020.00330

ISSN=2296-634X

ABSTRACT=<p>Pathogenesis of chronic obstructive pulmonary disease (COPD) is dependent on chronic inflammation and is hypothesized to represent organ-specific senescence phenotype. Identification of senescence-associated gene drivers for the development of COPD is warranted. By employing automated pipeline, we have compiled lists of the genes implicated in COPD (<italic>N</italic> = 918) and of the genes changing their activity along with cell senescence (<italic>N</italic> = 262), with a significant (<italic>p</italic> &lt; 7.06e<sup>–60</sup>) overlap between these datasets (<italic>N</italic> = 89). A mega-analysis and a partial mega-analysis were conducted for gene sets linked to senescence but not yet to COPD, in nine independent mRNA expression datasets comprised of tissue samples of COPD cases (<italic>N</italic> = 171) and controls (<italic>N</italic> = 256). Mega-analysis of expression has identified <italic>CD38</italic> and <italic>TNFRSF12A</italic> (<italic>p</italic> &lt; 2.12e<sup>–8</sup>) as genes not yet explored in a context of senescence–COPD connection. Functional pathway enrichment analysis allowed to generate a model, which explains accelerated aging phenotypes previously observed in COPD patients. Presented results call for investigation of the role of TNFRSF12A/CD38 balance in establishing a vicious cycle of unresolvable tissue remodeling in COPD lungs.</p>