Copd: What Causes the Lungs to Lose Their Ability to Heal? [STUDY]

In chronic obstructive pulmonary disease (COPD), the lungs lack the ability to repair damage on their own. Scientists at the Helmholtz Zentrum Munchen, partner in the German Center for Lung Research have discovered the reason for this deterioration.

The first symptom of COPD is usually a chronic cough. As the disease progresses, the airspaces narrow and more often develop pulmonary emphysema, which is an irreversible expansion and damage to the alveoli, or air sacks.

The research findings, published in the Journal of Experimental Medicine, blame the molecule Wnt5a for this problem. "The body is no longer able to repair the destroyed structures," lead researcher Dr. Melanie Konigshoff explains.

Konigshoff stated that they have been able to show that COPD results in a change in the messengers which the lung cells use to communicate with each other, according to Sciencedaily.

The scientists discovered an increase in the production of the Wnt5a molecule, which disrupts the classic Wnt/beta-catenin signaling pathway that is responsible for the repairs.

The study's first author and an LRR scientist, Dr. Hoeke Baarsma noted that their working hypothesis is that, the relationship between different Wnt messengers is no longer balanced in COPD.

The scientists searched for possible interference signals. In both the pre-clinical model and the tissue samples from patients, they found that in COPD tissue particularly the non-canonical Wnt5a molecule is increased and occurs in a modified form.

According to the authors, the stimuli that cause a reaction in COPD, such as cigarette smoke, leads to the additional increase in the production of Wnt5a and consequently impairs lung regeneration.

The team also demonstrated where the misdirected signal originates. Baarsma said that it is produced by certain cells in the connective tissue, the so called fibroblasts.

She added that, when pulmonary epithelial cells are treated with the Wnt5a which is derived from the fibroblasts, the cells automatically loss their healing ability.

The scientists were able to use antibodies directed against Wnt5a in two different experimental models to minimize the lung destruction and maintain improved lung function.

They noted that the results show that the classic Wnt/beta-catenin signal cascade is disrupted by the Wnt5a ligand. Konigshoff explains the importance of the result, she said it is a completely new mechanism in association with COPD and could lead to new therapeutic approaches, that are urgently needed for treatment.

According to Medicalexpress, the Wnt signaling pathway is one of many pathways used in forwarding signals in order to allow the cells respond to external changes. Numerous proteins are involved in the canonical forwarding of the signals, including beta-catenin as the central cellular messenger.

The signaling pathway is named after its main player "Wnt". It is a signaling protein that plays a key role in the development of various animal cells as a local mediator.

A pathway, in which Wnt acts through other messengers, is called a non-canonical signaling pathway which can have a negative impact on the canonical signaling.