Grant: Project Grant

Diabetes is characterized by high blood sugar and is often associated with several complications as a result of poor blood sugar control, the most serious complications including heart disease and kidney failure. People with kidney failure may require treatment by artificial kidney (dialysis) or by kidney transplant to survive. Despite the use of currently available medications to lower blood sugar and blood pressure, kidney function continues to decline in most people with diabetic kidney disease (DKD). New alternative treatments are therefore urgently needed. A molecule called hedgehog interacting protein (Hhip) is a key regulatory component of Hedgehog signalling, which controls organ development during gestation (in the womb) and optimizes cell functions in adults. Our recent work led to the discovery that high blood sugar levels turn on the Hhip expression in diabetic kidney, causing kidney damage. Most importantly, we found that urinary Hhip (uHhip) appears to be elevated in early DKD before the development of microalbuminuria (a hallmark of onset of kidney disease) in diabetic mice and humans with type 2 diabetes, suggesting that uHhip might be a novel indicator that could be used for the early detection of DKD, possibly identifying patients who will benefit from more intensive renoprotective interventions at an earlier stage indicator in DKD. However, several key questions regarding Hhip gene regulation, secretion and cell-to cell communication in responding to elevated glucose levels are poorly understood. My research program is to perform studies in kidney cells grown in petri dishes and in diabetic mouse models to answer these questions. Our studies will provide new insights into the processes how does Hhip causing kidney injury in diabetes and should provide new treatment strategies to prevent kidney damage in patients with diabetes mellitus.