Grant: Project Grant

Kidney disease caused by diabetes is the most common cause of kidney failure in Canada. Currently, the main treatments to stop kidney disease from getting worse in diabetes are medications that lower blood sugar levels and medications that lower blood pressure levels. Although these medications are helpful, they are only partly effective and we need new treatments. RNAs are small molecules that are present in all cells. It has been known for several decades that RNAs pass the genetic code from the DNA in our genes to make proteins, the workhorses of our cells. DNA carries the code for RNA and RNA carries the code for protein. More recently it has come to be appreciated that a large amount of our DNA makes RNA that does not carry a code to make proteins. These RNA molecules are called non-coding RNAs and they can be classified according to their length: long or short. Although long non-coding RNAs do not code for proteins they do have important roles in cells, like helping to turn genes on or off, acting as scaffolds or helping other RNA molecules to make proteins. Long non-coding RNAs often go wrong in disease but their contribution to the development of diabetic kidney disease is essentially unknown. Through our earlier work, we have discovered that the amount of a particular long non-coding RNA, called HOTAIR, is increased in diabetic kidney disease and that blocking its actions helps protect special kidney cells, called podocytes, from damage caused by high sugar levels. In this project, we will conduct a series of experiments to explore the role of HOTAIR in the development of diabetic kidney disease and to determine whether blocking HOTAIR can protect against kidney damage. These studies will provide important new information about the previously underappreciated actions of non-coding RNA in diabetic kidney disease, with long non-coding RNA blocking therapy being a plausible new treatment for the condition.