Grant: Project Grant

Chronic kidney disease is a common problem, affecting about 11% of Canadians. We previously studied proteins that belong to the family of activin proteins. Blocking activins A and B improves chronic kidney disease. A third member of the family is activin C was thought to be mostly present in the liver. Activin C is made up of two proteins called inhibin beta C which are stuck together. We found that inhibin beta C is in fact present in the kidney tubules. We also found inhibin beta C is increased in the blood of people with chronic kidney disease, and in the blood and urine of mouse models of chronic kidney disease. Complicating matters, inhibin beta C can not only stick to another inhibin beta C to make activin C, but can also stick to other proteins to make activins AC and BC. Each of these may have different function in the kidneys. In our studies, we will test to see which of these is made in the kidney, and which is found in the blood and kidney in mice and people with chronic kidney disease. We found that activin C causes kidney tubular cells to make more scar proteins. We will test the functions of activins AC and BC if we find them to be increased. We will test the importance of inhibin beta C to kidney fibrosis in mice that are made to not have any inhibin beta C, as well as in mice that we cause to have much higher inhibin beta C levels in blood than normal. Using these, we will see if changing inhibin beta C levels makes a difference to kidney function and kidney scarring. In understanding if inhibin beta C is important in chronic kidney disease, and what protein it forms to do this, we may be able to develop treatments to stop its function or to use it as a test to tell which people may be at higher risk of developing worsening of their kidney disease.