Scientists have provided the first evidence that an enzyme called Eya1
protein phosphatase is a critical regulator of lung function and that
this may have broad implications for sufferers of a variety of pulmonary
diseases. "Identification of the role of Eya1 in establishing pulmonary
tight junction and barrier integrity could have a significant impact on
asthma, chronic obstructive pulmonary disease, and acute respiratory
distress syndrome, all diseases characterized with disruptions in
permeability," said Ahmed El-Hashash, PhD, investigator at The
Saban Research Institute of Children's Hospital Los Angeles and
assistant professor at the Keck School of Medicine.
Proper formation of lung epithelium is essential to life. The 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, a life-threatening lung
condition that prevents adequate oxygen from getting from the lungs and
into the blood.
Until now, very 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,
and El-Hashash provided the first evidence that the enzyme Eya1 protein
phosphatase controls tight junction and permeability barrier formation
in the lung epithelium. They have 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
"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.
Children's Hospital Los Angeles