Supported Research

Lay Summary
Hypertension and diabetes are leading causes of chronic kidney disease and both have reached epidemic status worldwide. Despite the many efforts aimed at understanding the pathogenesis of hypertensive kidney disease, to this day the therapeutic approaches are inadequate. Novel targets are needed to effectively manage disease outcomes.
 
Prostaglandin-E2 (PGE2) is a hormone-like substance that is released by blood vessel walls in response to infection or inflammation. In the kidney, it regulates blood flow in the glomerulus (kidney component responsible for filtration), renin (enzyme that controls blood pressure) secretion, and tubular transport (process by which solutes and water are removed from the tubular fluid and transported into the blood), via four PGE2-EP receptor subtypes (EP1-4). In general, two receptor subtypes, namely EP1 and EP3 promote disease processes, but the receptor subtypes EP2 and EP4 are beneficial. Dr. Hebert showed that the receptor subtype EP1 or EP3 deletion prevents diabetic hyperfiltration, kidney growth, and proteinuria (presence of protein in urine) in diabetic mice. The EP3 receptor deletion attenuates the excessive or an abnormally large production of urine by improving urine concentrating function. Whether protective effects of this receptor subtype EP1 or EP3 deletion apply to hypertensive kidney disease is unknown.
 
Dr. Herbert’s lab has produced a mice model to be able to study the different role of these receptors in the hypertensive kidney. His project will clarify the importance of EP3 receptor in the absence of EP1 receptor, in preventing water and sodium disturbances in the mice model.