About This Project

Lungs are still developing when a premature baby is born. If the lungs are damaged by O2 and ventilators, the Type I cells that are supposed to line the developing alveoli may produce too much free RAGE, a protein normally on the surface of the Type I cell. This RAGE will adhere to the growing lung scaffold or matrix at sites where the Type I cells are supposed to attach. This prevents the Type I cells from developing normally and can lead to chronic lung damage or bronchopulmonary dysplasia.

Ask the Scientists

What is the context of this research?

RAGE is a protein on the surface of Type I cells with roles in normal and injured lungs. Lung RAGE and soluble RAGE (sRAGE) levels are in patients with COPD and acute respiratory distress. We know that excess RAGE in embryos cause incomplete development of the lungs. In neonatal mice extra RAGE leads to simplified alveoli. In adult mice, too much RAGE leads to emphysema. Cultured lung cells with extra RAGE stick better to matrix proteins.

Our pilot studies show newborn mouse Type I cells produce more inflammation than in adult mouse cells. We found sRAGE in tracheal samples from premature infants with lung injury as well as autopsy specimens from babies with severe lung disease. This experiment will test whether increased sRAGE prevents Type I cells from attaching normally.

What is the significance of this project?

Over 15,000 babies born prematurely each year develop bronchopulmonary dysplasia (BPD). They are at risk of long hospital stays, poor growth and developmental delay. Finding out why damaging the preterm lung leads to the alveolar simplification seen in BPD can lead to new preventive and therapeutic approaches. Up to now, there has been little work done on the cells that line the alveoli, the Type I cell, because until recently it was difficult to study pure samples of these cells. Our lab is one of the first to look at newborn and preterm Type I cells. What we learn may have a profound impact in fragile babies and families in the future.

What are the goals of the project?

The funds raised will be used to pay for the supplies and lab facilities to determine if increased amounts of sRAGE decrease Type I cell attachment.

Specifically, similar numbers of Type I cells from newborn or adult lungs will be added to culture wells coated with different extracellular matrix proteins. Within each series of wells, increasing amounts of sRAGE will be added at the same time. After 24 hours, the number of cells attached to the matrix will be counted and the effect of extra sRAGE on attachment assessed. We will also compare newborn to adult cell attachment, and the role of different matrix proteins.

The results will be important for our applications for more grants from the NIH, March of Dimes and other foundations.