The anti-inflammatory molecule protectin DX (PDX) has been shown to improve pulmonary fibrosis (PF) and lung function in mice, new research shows.
The study, “Posttreatment with Protectin DX ameliorates bleomycin-induced pulmonary fibrosis and lung dysfunction in mice,” was published in the journal Scientific Reports.
Lung fibrosis is characterized by uncontrolled accumulation of extracellular matrix (constituted by molecules that provide cellular scaffolding and participate in tissue stability). This process can lead to permanent lesions, impairment of pulmonary function, and cause progressive difficulty in breathing. Ultimately, patients may die from respiratory failure.
Despite the severity of lung fibrosis and its occurrence in most chronic lung diseases, few treatment strategies – if any – are available.
PDX is an endogenous molecule that is believed to exert anti-inflammatory and immune-regulatory actions. Recent studies have shown that PDX protects against oxidative stress and inhibits blood platelet aggregation. However, the therapeutic potential of PDX in pulmonary function remained unknown.
Now, a research team led by Shengwei Jin, and MD and PhD at the Second Affiliated Hospital of Wenzhou Medical University in China, studied the effect of treatment with PDX in a mouse model of PF. The experiments included a combination of in vitro and in vivo assessments.
The scientists observed that PDX treatment improved inflammatory responses and the levels of pro-inflammatory cytokines related to fibrosis. PDX was also able to reverse the extracellular matrix accumulation and histological changes. The drug shows benefits in lung function, improved levels of oxygen in the blood, and prolonged the life span of mice.
Of note, a potential mechanism promoting fibrosis resolution and decreasing cells’ migratory capacity, invasiveness, and elevated resistance was observed. The mechanism involves an improvement in the altered levels of proteins that form the extracellular matrix, and are involved in cell binding in tissues and modulating cell shape.
Overall, although additional studies are necessary to better understand the effects of PDX, the results show that treatment with this agent shows an improvement in PF and lung dysfunction in mice.
“These data have significant implications for future efforts in developing an efficient therapeutic strategy for treating lung fibrosis by targeting PDX actions,” the researchers wrote.
Other compounds have been shown to inhibit inflammation and prevent fibrosis using the same animal model. However, they failed to prevent subsequent tissue destruction and dysfunction. The results seen with PDX highlight the benefit of a post-treatment strategy rather than aiming for prevention of fibrosis.
This is an important aspect, “given that in clinical use [it] is often more important when the fibrotic changes of various etiologies are already apparent in the patient,” according to researchers.