The Kidney Foundation of Canada

Dr. Joan Krepinsky 

Dr. Joan Krepinsky

McMaster University, ON

Role of miR-299a in regulating renal fibrosis

Co-applicant(s): Neel Mehta

2018-2020:  $100,000 |  Biomedical Research Grants  |  Category: Hypertension

Lay Summary

In patients with chronic kidney disease, the filtering units of the kidney, (called glomeruli), develop scars. As these scars become larger the kidney is no longer able to function properly and eventually patients will need to have either dialysis or a kidney transplant to survive. The protein TGFbeta is an important cause of this scarring. It makes cells found in these filtering units – called mesangial cells – produce scar proteins. Blocking TGFbeta actions in patients would offer a way to slow or prevent the decrease in kidney function that is often seen in patients with chronic kidney disease.

Our studies show that a molecule called miRNA-299a-5p is important to allowing TGFbeta to work in kidney mesangial cells. Blocking miRNA-299a-5p can prevent kidney mesangial cells from responding to TGFbeta and from making scar proteins. In kidneys taken from mice with chronic kidney disease, miRNA-99a-5p is increased. This suggests that miRNA-299a-5p is an important player in kidney scarring. In our studies, we would like to understand how miRNA-299a-5p allows TGFbeta to direct kidney mesangial cells to make scar proteins, and whether blocking the function of miRNA-299a-5p will prevent kidney scarring and help to prevent kidney function from getting worse in mice with chronic kidney disease. Drugs which block other molecules like miRNA-299a-5p have already been used successfully in patients. If our studies show that blocking miRNA-299a-5p prevents kidney scarring and helps to keep kidney function from getting worse over time, this will give us a new treatment to test in patients with chronic kidney disease.

Biography

I am a clinician-researcher with the Division of Nephrology, McMaster University. I see patients with general kidney problems, chronic kidney disease and kidney failure who are being treated with dialysis. My research goal is to better understand the process of kidney scarring in chronic kidney disease, especially that associated with high blood pressure. This is because kidney scarring over time builds up and leads to failure of kidney function. The focus of my current work funded by the Kidney Foundation of Canada is to evaluate the role of a particular molecule (micro RNA) in the scarring process, and to test whether blocking this micro RNA will improve kidney function and decrease scarring in a model of chronic kidney disease associated with high blood pressure.