Published by the Students of Johns Hopkins since 1896
April 16, 2024

HGF improves damaged alveoli by binding to MET

By CAROLYN ZIN | March 7, 2013

Revenge against emphysema, a deadly and overbearing disease, has been strategically plotted in order to defend and protect the lives of the more than 20 million Americans engaged in a battle with the disease. Thankfully, researchers have discovered ways to ameliorate symptoms that are presented in emphysema patients.

The third-leading cause of death in the United States is chronic obstructive pulmonary disease (COPD), which includes diseases like emphysema. These diseases are not only caused by smoking but also by exposure to toxic dusts and fumes. Patients with emphysema have difficulty breathing due to the destruction of the alveoli compartments responsible for the intake of oxygen. Lungs infected with emphysema or similar diseases also have an accelerated form of cell death and difficulty with cell renewal.

“The diseases that are most challenging for us to treat are the diseases where you get a loss or scarring of part of the lung we call the alveoli compartment, where the oxygen crosses into the bloodstream. Basically, you need to have a certain number of alveoli in your lungs so that enough oxygen gets into your bloodstream so that you can get the proper oxygenation of all your vitals,” Enid Neptune, associate professor of Pulmonary and Critical Care medicine at the Hopkins School of Medicine, explained.

Neptune and her team of researchers have made significant progress on the battle against emphysema, as they found possible ways to improve the function of damaged alveoli. Several experiments have been performed using the hepatocyte growth factor, known as HGF, to regrow the damaged alveoli and restore their function.

“We looked at HGF because it was able to do all of the types of activities that one would need if you needed to grow new alveoli. A molecule that has these behaviors and pathway has some evidence of therapeutic utility. HGF just had the full spectrum that we were looking for,” Neptune added.

Experiments were carried out in small animal models to test the effectiveness of HGF. Half of the mice with emphysema were injected with HGF for two weeks, while the other half of the mice were injected with a placebo. Mice with normal lung functions served as the control group.  Similarly, HGF was injected into half of the control group while the other half was injected with a placebo.

Results were promising, as there was noticeable improvement in the lung function of the subjects. There was a 17 percent increase in the size of the air sacs in the emphysema group injected with HGF, which signifies an improvement in lung function. Thus, the HGF proved effective in treating the damaged alveoli.

Furthermore, the efficiency and success in using HGF in subjects with emphysema drove Neptune’s team to test the role of HGF in the underdeveloped lungs of young subjects. In another experiment, an HGF receptor called MET was removed from cells in the alveoli. As expected, when MET was removed, there was damage to the alveoli, indicating that in order for developing lungs to function normally, they require HGF to bind to MET.

Neptune and her team are making great strides towards utilizing HGF in other subjects, as they look for ways to make the delivery of HGF more efficient.

“We are focusing on trying to package HGF so that we might potentially be able to deliver it directly into the lungs. If we can be successful doing that in a mouse model, we can potentially escalate that to larger models. The other thing is to explore small molecule activators of the pathway. They would potentially allow you to get a very efficient level of receptor activation. We are pursuing both of those avenues with the hope that we will have something in the pipeline in the near future,” Neptune said.


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