Published October 2015
The FASEB Journal

Even though lung biologists have a relatively deep understanding of the molecular mechanisms that regulate embryonic and fetal lung development, they understand less about the development and growth of the postnatal lung.

A study led by Brian Varisco, MD, identified a role for chymotrypsin-like elastase 1 (Cela1) protein in remodeling lung elastin in a stretch-dependent manner. Protein-level expression of Cela1 had previously been demonstrated only in the pancreas. The findings appeared October 2015 in The FASEB Journal.

Knowing that the postnatal lung is constantly exposed to cyclic stretch, the team used normal mouse lung development, the mouse pneumonectomy model of lung regeneration, and living mouse lung sections to test whether the expression and binding of Cela1 were stretch-dependent.

Among the results: Cela1 protein increased 176-fold during lung development, and an additional three-fold during lung regeneration. Stretch increased Cela1 binding to lung elastin by 46 percent. This binding occurred in areas of increased elastin remodeling.

Cela1 also was expressed in a subset of lung cells that reside in regions where multiple airspace walls come together. This indicates that Cela1 may play an important postnatal role in stretch-dependent remodeling of the peripheral lung.

The team also found that the protease of Cela1 is neutralized by the Serpina1 (a-1-antitrypsin), a protein-coding gene associated with progressive emphysema. Thus, Cela1 may play a role in distal lung development and regeneration as well as in the airspace destruction triggered by alpha-1-antitrypsin deficiency.

Says Varisco: “These findings may lead to novel therapies targeting Cela1 in diseases of congenital or acquired distal airspace simplification."