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Mechanism Critical to Lung Formation and Regeneration Identified

Scientists have provided the first evidence that an enzyme called Eya1 protein phosphatase is a critical regulator of lung function, which may have broad implications for sufferers of a variety of pulmonary diseases.

 Proper formation of lung epithelium is essential to life. Normal growth and functioning of the lung depends on the formation of tight junctions between adjacent cells making up the alveolar epithelial sheet, a thin layer of tissue separating neighboring alveoli. Alveoli are the site of gas exchange between the lung and blood vessels. Loss of these tight junctions alters the exchange of oxygen and carbon dioxide. Permeability dysfunction has been implicated in both acute lung injury and acute respiratory distress syndrome.

Until now, little has been known about the basic regulatory mechanisms underlying permeability barrier formation and integrity of the lung epithelium. David Warburton, MD, director of Developmental Biology and Regenerative Medicine at The Saban Research Institute of Children's Hospital Los Angelos, and Ahmed El-Hashash, PhD, investigator at the same university and assistant professor at the Keck School of Medicine, provided the first evidence that the enzyme Eya1 protein phosphatase controls tight junction and permeability barrier formation in the lung epithelium. They also provided the first evidence that Eya1 enzyme coordinates a complex network of other cellular proteins and molecules that are essential for epithelial barrier integrity and are therefore critical to optimal lung function. Both in vivo and in vitro experiments showed that interfering with Eya1 phosphatase function resulted in defective formation of tight junctions and the permeability barrier.

"These findings identify a novel therapeutic option for lung diseases like COPD and ARDS," said Warburton. "Our discovery of Eya1 enzyme control of pulmonary barrier integrity suggests that influencing alveolar epithelial junction formation by manipulating the activity of enzymes has the potential to identify future targets for the treatment of lung injury and may provide solutions to the problems concerning regeneration of lung tissue for restoration of functional alveoli."

Results of the study will be published in the Journal of Cell Science.

Source: Children's Hospital Los Angeles

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