Modulation des processus dégénératifs et apoptotiques induits par le proNGF dans les troubles mictionnels reliés au diabète

 

Lysanne Campeau

CIUSSS du Centre-Ouest-de-l'Île-de-Montréal

 

Domaine : vieillissement

Programme Chercheurs-boursiers cliniciens - Junior 2

Concours 2019-2020

A majority of diabetics suffer from voiding problems that can range from urgent need to urinate to severe health problems such as infections and kidney failure. The premature form of nerve growth factor (proNGF) is a protein found throughout the body and is found to increase in diabetes, with an involvement in many of its complications. ProNGF binds to a receptor called p75, with both of them found in the bladder.

Our initial studies showed that type 1 diabetic mice treated with a drug to block proNGF had better bladder function and structure compared to diabetic untreated mice. So far, there are no studies to explore the harmful effect of proNGF on bladder function in diabetic conditions.

In this study, we aim to identify the role of proNGF and p75 in bladder dysfunction associated with diabetes and to show the therapeutic effect of blocking proNGF/p75 interaction in its management. First, we will study the effect of proNGF/p75 on bladder cells and identify their response in terms of survival and signaling pattern. Then, we are going to inject type 2 diabetic mice with newly developed drugs to block the effect of proNGF and p75. We will study how this approach would prevent diabetic complications in the bladder by testing its function and structure. Lastly, we will prevent the production of p75 in specific bladder cells in type 1 diabetic mice, and study how this receptor impacts the progression of bladder dysfunction according to bladder cell type.

This study will uncover a possible mechanism explaining bladder dysfunction in diabetes, and help develop drugs to treat this serious health problem affecting thousands of diabetic patients in Quebec.