Study: Cigarette Smoke Prevents Self-Healing in the Lungs

A new study found that cigarette smoke exposure downregulated WNT receptors Frizzled (FZD4), which, in turn, was associated with impairment of the lung’s self-healing process in patients with chronic obstructive pulmonary disease (COPD).

The study used lung tissue from never-smokers, smokers, and patient with COPD to identify and characterize the mechanisms associated with impaired healing function in the lungs caused by reduced WNT/β-catenin signaling.
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Researchers found that FZD4 expression was reduced in primary ATII cells from COPD patients and in human and experimental COPD lung tissue. Likewise, cigarette smoke exposure downregulated FDZ4 expression in vitro and in vivo, and reduced WNT target gene expression.

“Inhibition of FZD4 decreased WNT/β-catenin activity and epithelial cell proliferation, and interfered with ATII to [alveolar epithelial type I] cell trans-differentiation, whereas FZD4 overexpression augmented WNT/β-catenin signaling and epithelial cell proliferation,” the researchers wrote.

In addition, FZD4 overexpression in lung tissue reduced the effects of cigarette smoke on decreased elastin expression.

“Reduced FZD4 expression in COPD contributes to impaired alveolar repair capacity. Thus, FZD4 represents a potential therapeutic target for COPD,” the researchers concluded.

—Melissa Weiss

Reference:

Skronska-Wasek W, Mutze K, Baarsma HA, et al. Reduced frizzled receptor 4 expression prevents WNT/β-catenin-driven alveolar lung repair in COPD [published February 28, 2017]. Am K Respir Crit Care Med. doi:http://dx.doi.org/10.1164/rccm.201605-0904OC.