Researchers believe that a protein called Wnt5A may be the cause of why the lungs of patients with chronic obstructive pulmonary disease (COPD) lose the ability to repair themselves. The study that contains those findings, “Non-canonical WNT-5A signaling impairs 1 endogenous lung repair in COPD,” was published in the Journal of Experimental Medicine.
COPD is a leading cause of death worldwide. One main pathological feature of COPD is the loss of functional alveolar tissue without adequate repair (emphysema). But the the underlying mechanisms of that decline are poorly defined.
Reduced Wnt5A (WNT–β-catenin) signaling is linked to impaired lung repair in COPD, However, until now the factors responsible for attenuating this pathway remained unclear.
“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 this study, research team found that an increased production of the Wnt5a molecule that disrupts the classic (also termed as “canonical”) Wnt/beta-catenin signaling pathway is responsible for the lack of such repair.
“Our working hypothesis was that the relationship between different Wnt messengers is no longer balanced in COPD,” said Hoeke Baarsma, PhD, the study’s first author.
The researchers also looked for potential signals interfering in the process. “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,” they wrote.
Cigarette smoke and other stimuli that cause a reaction in COPD also contribute to an increased production of the Wnt5a molecule, and subsequently to an impaired lung repair.
In their experiments on animals, the researchers discovered where the interference signal begins: “It is produced by certain cells in the connective tissue, the so-called fibroblasts,” Baarsma said.
When the researchers treated pulmonary epithelial cells with the Wnt5a molecule originated from the fibroblasts, the cells lost their capacity to repair. Using two different models, the researchers used antibodies targeting Wnt5a and observed that they were able to slow down the destruction of the lung and keep a better 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,” Königshoff concluded.
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