February 23, 2017

A target to heal tiny lungs

The protein beta-catenin may be a good target for therapies to treat lung disease that is a common complication of preterm birth.

(iStock)

Bronchopulmonary dysplasia (BPD) – a form of chronic lung disease – is a common complication of preterm birth and results from airway injury during a certain stage of lung development.

Jennifer Sucre, M.D., and colleagues hypothesized that a signaling pathway active during lung development – the Wnt/beta-catenin pathway – may play a role in the pathophysiology of BPD. The researchers found a marker of active Wnt signaling, nuclear phosphorylated beta-catenin, in fetal and preterm BPD lung tissue, but not in lung tissue from full-term infants.

Using a 3D human organoid model they developed, the investigators demonstrated that oxygen conditions that cause BPD-related cellular changes resulted in increased levels of nuclear phosphorylated beta-catenin. They found that inhibitors of the phosphorylation blocked the nuclear localization of beta-catenin and the BPD-related cellular changes.

The findings, reported in the February American Journal of Physiology – Lung Cellular and Molecular Physiology, support a role for Wnt/beta-catenin signaling in BPD and suggest that beta-catenin may be a relevant therapeutic target for this disease.

This research was supported by grants from the National Institutes of Health (HD087023, GM114259, GM108087). Jennifer Sucre received a Clinical Fellowship Training Grant from the Eli and Edythe Broad Center of Regenerative Medicine at UCLA, and the California Institute of Regenerative Medicine provided additional support.

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