Grant: Project Grant

People who have diabetes while they are pregnant are more likely to have children at risk for developing asthma later in life. Asthma causes the airways of the lung to become twitchy and narrow too much. Like breathing through a straw, these smaller airways make it hard for people to get full breaths. The twitchiness of the airways is caused by a specific cell, airway smooth muscle. Our lab has shown that, in mice, exposure to diabetes during pregnancy increases the twitchiness of the airways, resulting in difficulty breathing. We do not know, however, why diabetes during pregnancy makes the airways twitchier or if we prevent this change from occurring in kids exposed to diabetes during pregnancy. One possibility is that the high blood glucose during pregnancy changes the way the smooth muscle cells function, making them stronger and more able to narrow the airways. To test this theory, we will use mice and stem cells to understand whether maternal diabetes makes the smooth muscle around the airways stronger, and if high-glucose in the womb is enough to cause these changes. We will also measure changes in the action of a specific enzyme (RhoA) that could coordinate these changes. With this information, our team will better understand how diabetes during pregnancy makes airways twitchier in asthma. We will also learn whether reducing blood glucose levels during pregnancy is an effective way to prevent these changes from occurring. This information may allow us to stop asthma from developing before it is a problem that requires medicine to treat.