Activin C signalling in the pathogenesis of acute kidney injury: The regulatory role of Erk5
Lay Abstract
Studying how a protein called Erk5 protects against kidney injury. Many people develop kidney injury in hospital, especially those that are sick enough to be admitted to the intensive care unit. This is called acute kidney injury (AKI). It not only is associated with a higher risk of dying in hospital, but it can also lead to a greater chance of developing kidney disease and kidney failure months or years afterwards. The most common cause of AKI is reduced blood flow to the kidneys. We have been studying proteins called activins A and B which contribute to kidney damage in AKI and in chronic kidney disease. There are several related but somewhat different proteins in the activin family. Not much is known of a third member called activin C, but we found that it is present in certain parts of the kidney tubules which are most injured by low blood flow (ischemia). We have mice that do not have activin C expressed in the kidneys. We found that these mice are protected from kidney injury after ischemia. We also found that the kidneys without activin C have more of a protein called Erk5. This protein is important to protecting other organs from different kinds of stress. In our studies, we will investigate whether Erk5 protects kidneys from injury from ischemia, and how it does this. We will also study how it regulates the injury that is caused by activin C. With this understanding, we may be able to develop treatments to help improve AKI and progression to chronic kidney disease after AKI.
