Abstract
Chronic obstructive pulmonary disease (COPD) is a devastating, irreversible pathology affecting millions of people worldwide. Clinical studies show that currently available therapies are insufficient, have no or little effect on elevated comorbidities and on systemic inflammation. To develop alternative therapeutic options, a better understanding of the molecular background of COPD is essential. In the present study, we show that non-canonical and pro-inflammatory Wnt5a is up-regulated by cigarette smoking with parallel up-regulation of pro-inflammatory cytokines in both mouse and human model systems. Wnt5a is not only a pro-inflammatory Wnt ligand but can also inhibit the anti-inflammatory peroxisome proliferator-activated receptor gamma transcription and affect M1/M2 macrophage polarization. Both Wnt5a and pro-inflammatory cytokines can be transported in lipid bilayer sealed extracellular vesicles that reach and deliver their contents to every organ measured in the blood of COPD patients, therefore, demonstrating a potential mechanism for the systemic nature of this crippling disease.
Highlights
Chronic obstructive pulmonary disease (COPD) is an irreversible condition of airflow limitation characterized by inflammation and impaired respiratory gas exchange [1]
The test animals developed emphysema-like tissue damage (Figure 1A) that correlated with decreased epithelial cell number (Figure 1B)
The Cigarette smoke extract (CSE) treated aggregates have shown increased levels of Wnt5a both at mRNA and protein levels but only if monocytes were present in the aggregate tissues (Figures 2A–D) [45, 46]
Summary
Chronic obstructive pulmonary disease (COPD) is an irreversible condition of airflow limitation characterized by inflammation and impaired respiratory gas exchange [1]. Based on recent statistics, COPD is the seventh and fourth highest cause of disability and death worldwide, respectively [3]. The main cause of COPD is tobacco smoking, but other factors, such as air pollution, occupational hazards, and infections can initiate the disease [4, 5]. Despite all the therapeutic efforts, COPD is not just irreversible but is progressive in nature [6]. COPD is recognized primarily as a lung disease, it has systemic manifestations and the comorbidities affect the heart, pancreas, skeletal muscle, and other organs [7]. Apart from the limited efficacy, unwanted side effects occur including histone deacetylase regulated resistance to corticosteroids [11, 12]
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