Although chronic obstructive pulmonary disease (COPD) remains a leading cause of death around the world, the reason for why patients with COPD lose the ability to repair damage to their lungs is poorly defined. However, researchers at the Helmholtz Zentrium MÃ¼nchen may now have an idea of why this happens.
Although chronic obstructive pulmonary disease (COPD) remains a leading cause of death around the world, the reason for why patients with COPD lose the ability to repair damage to their lungs is poorly defined. However, researchers at the Helmholtz Zentrium München may now have an idea of why this happens.
Research published in Journal of Experimental Medicine identify the molecule Wnt5a as the reason for irreversible damage to the alveoli that occurs as the disease progresses, airways narrow, and pulmonary emphysema develops. At this point, the body is unable to repair the destroyed air sacks, explained Melanie Königshoff, MD, PhD, head of the Research Unit Lung Repair and Regeneration at the Comprehensive Pneumology Center of Helmholtz Zentrum München.
"In our current work we have been able to show that COPD results in a change in the messengers that lung cells use to communicate with one another," Königshoff said in a statement.
According to the researchers, increased production of Wnt5a disrupts the Wnt/beta-catenin signaling pathway that would be responsible for repairing the damage. The study’s first author, Hoeke Baarsma, PhD, explained that their hypothesis was that there was an imbalance between Wnt messengers in patients with COPD. That meant searching for the interference.
"In both the pre-clinical model and the tissue samples from patients, we found that in COPD tissue particularly the non-canonical Wnt5a molecule is increased and occurs in a modified form,” said Baarsma.
Cigarette smoke and other stimuli that can cause a reaction in COPD increase the production of the Wnt5a molecule, thus resulting in impaired lung regeneration. The researchers went 1 step further and identified where the misdirected signal originates: cells in the connective tissue, the so-called fibroblasts. When Wnt5a derived from the fibroblasts were applied to pulmonary epithelial cells, they lost their ability to heal. In addition, using antibodies against the Wnt5a molecule actually slowed down lung destruction and better maintained lung function.
“Our results show that the classic Wnt/beta-catenin signal cascade is disrupted by the Wnt5a ligand,” said Königshoff. “This is a completely new mechanism in association with COPD and could lead to new therapeutic approaches, which are urgently needed for treatment.”