Page 24 - H. Cell signaling

[H. Cell signaling-19]

Protein acetylation-dependent pathological macrophage

activation drives fine particulate matter-induced chronic

obstructive pulmonary disease

Myungkyung Noh¹˙#, Jeong Yeon Sim¹˙#, Ho-Young Lee¹˙*

¹College of Pharmacy, Seoul National University, Seoul 08826, Korea

Substantial epidemiological evidence implicates fine particulate matter (PM) as a critical risk factor on respiratory
health, with particular reference to chronic obstructive pulmonary disease (COPD). Taking the needs to provide
effective therapeutic strategy for this deadly disease, we investigated the pathological mechanism of PM-induced

COPD. Mice chronically exposed to PM manifested severe COPD, marked by airway remodeling and alveoli
destruction. Importantly, the pathogenesis was accompanied by significant increase in leukocytes, and among them,

macrophages were the primary mediator of disease progression. Further transcriptome-wide analysis demonstrated
that post-translational protein acetylation was the most upregulated signature, and through this pathway,

macrophages were reprogrammed into pathologically activated status. To finally target this process for therapy, we
employed EM-Gp, which can regulate the mediators of protein acetylation. As expected, EM-Gp successfully

alleviated PM-induced COPD, by reverting macrophage polarization in protein acetylation-dependent manner. Taken
together, we identified the central mechanism driving PM-induced COPD, and suggested that targeting this pathway

with EM-Gp can be a powerful strategy for the disease treatment.