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Lung regeneration closer to reality with new discovery by Weill Cornell Medical College researchers
Date:10/28/2011

blood vessel cells.

The scientists found that removal of the left lung activates receptors on lung endothelial cells that respond to vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2). Activation of these receptors promotes the rise of another protein, matrix metalloproteinase-14 (MMP14). The researchers discovered that MMP14, by releasing epidermal growth factors (EGF), initiates the generation of new lung tissue.

When the investigators disabled receptors of VEGF and FGF-2 specifically in the endothelial cells of the mice, the right lung would not regenerate. The defect in the lung regeneration was found to be due to the lack of MMP14 generation from the blood vessels. Remarkably, when these mice received an endothelial cell transplant from a normal mouse, the production of MMP14 was restored, triggering the regeneration of functional alveoli.

"The recovery of lung function and lung mechanics by transplantation of endothelial cells that stimulate MMP14 production may be valuable for designing novel therapies for respiratory disorders," says Dr. Stefan Worgall, who helped with the functional lung studies in this project. "This study will also help us understand mechanisms for repair in the growing lungs of infants and children," he adds. Dr. Worgall is associate professor of pediatrics and genetic medicine and distinguished associate professor of pediatric pulmonology.

Given MMP14's role, Dr. Rafii classifies it as a crucial "angiocrine" signal -- a lung endothelial specific growth factor responsible for alveolar regeneration. Dr. Rafii's team also seeks to reveal the initiation signals resulting in the activation of lung blood vessels. "Changes in local blood flow and biomechanical forces in the remaining lung after removal of the left lung could certainly be one of the initiation cues that induce endothelial activation," says Dr. Sina Rabbany, who is a co-senior author of this study and a pro
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Contact: John Rodgers
jdr2001@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Source:Eurekalert

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