Berlin: Scientists have decoded how the lungs of chronic obstructive pulmonary disease (COPD) patients lose the ability to repair damages on their own.
Researchers at the Helmholtz Zentrum Munchen in Germany found that the molecule Wnt5a may be to blame for this problem.
The first indication of COPD is usually a chronic cough. As the disease progresses, the airways narrow and often pulmonary emphysema develops.
This indicates irreversible expansion and damage to the alveoli, or air sacks in the lungs.
The body is no longer able to repair the destroyed structures," said Melanie Konigshoff from the Helmholtz Zentrum Munchen.
"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," Konigshoff said. Scientists discovered increased production of the Wnt5a molecule, which disrupts the classic (or canonical) Wnt/beta-catenin signalling pathway that is responsible for such repairs. "Our working hypothesis was that the relationship between different Wnt messengers is no longer balanced in COPD," said Hoeke Baarsma, scientist at Research Unit Lung Repair and Regeneration (LRR) of Helmholtz Zentrum Munchen.
The team correspondingly searched for possible interference signals.
"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.
According to the researchers, stimuli that typically cause a reaction in COPD, such as cigarette smoke, additionally lead to increased production of Wnt5a and consequently to impaired lung regeneration.
In the next step, the researchers were able to show where the misdirected signal originates: "It is produced by certain cells in the connective tissue, the so-called fibroblasts," Baarsma said.
When pulmonary epithelial cells were treated with the Wnt5a derived from the fibroblasts, the cells lost their healing ability.
The scientists were also able to use antibodies directed against Wnt5a in two different experimental models to slow down the lung destruction and better maintain the lung function.
"Our results show that the classic Wnt/beta-catenin signal cascade is disrupted by the Wnt5a ligand. This is a completely new mechanism in association with COPD and could lead to new therapeutic approaches, which are urgently needed for treatment," Konigshoff added. The study was published in the Journal of Experimental Medicine.