Grant: Project Grant

Long-term exposure to harmful substances like unhealthy diets can damage the liver over time. This ongoing damage activates special liver cells called hepatic stellate cells (HSCs). Normally, these cells are inactive and store vitamin A. But when they're activated by liver injury, they lose this function and turn into scar-forming cells, producing proteins that build up and cause liver scarring, known as fibrosis. Liver fibrosis affects millions of people worldwide and can lead to cirrhosis, severe liver damage that is a major cause of death globally. The rise in obesity and alcohol use has made these liver diseases even more common. Unfortunately, there are currently no approved drugs that can reverse fibrosis, and the only treatment for advanced cirrhosis is a liver transplant. This makes finding new treatments extremely important. One potential approach is to break down the excess scar tissue in the liver. This process is controlled by certain proteins called matrix metalloproteinases (MMPs). Our previous research showed that one of these proteins, called MMP14, plays a role in how the liver processes fat. We also found that MMP14 levels increase in damaged livers, but its role in liver scarring wasn't clear. In mouse studies, we discovered that removing MMP14 from liver cells did not make scarring worse. However, removing it from hepatic stellate cells made the scarring worse. This suggests that MMP14 plays different roles depending on the cell type. We are now studying how MMP14 in both liver cells and stellate cells affects liver damage. These studies may help uncover new targets for therapies to treat or reverse liver fibrosis and restore liver health.