Understanding how remodeling of the ECM and altered cell-substrate interactions facilitate progression of tubulointerstitial fibrosis
Recent studies suggest that glucose levels and stress molecules can change cell surroundings, disrupting the kidney cells’ ability to talk to each other. Professor Squires would like to understand how high glucose levels and stress molecules do this in the kidney and why it leads to kidney disease. This study will help us understand how kidney disease develops and inform the future development of new treatments.
Background to research
In diabetes, high glucose levels add stress to kidney cells and make it harder for them to work properly. Kidney cells move apart, lose contact with each other and fail to detect danger signals when they arise.
Professor Squires and his team has previously shown that high glucose levels reduce the stickiness between kidney cells. They also found that kidneys from people with diabetes had different levels of particular molecules, responsible for carrying signals from one kidney cell to the other. When the cells can’t communicate with each other, they lose the ability to work together efficiently. However, we still don’t fully understand how exactly the environment around kidney cells, also known as extracellular matrix, changes as a result of stress and high glucose levels.
A PhD student in Professor Squires’ laboratory plans to find out how in the environment around kidney cells changes, and how this prevents kidney cells from communicating with each other. They will use cells from healthy kidneys and from kidneys affected by diabetes to find the differences between the two.
Professor Squires and his student will be using state-of-the-art techniques to study the behaviour of single cells. This way, they hope to find out how vital information is passed from one cell to another, both in healthy kidneys and kidneys affected by diabetes. They’d like to uncover the identity of specific molecules needed to keep kidney cells healthy and happy.
Potential benefit to people with diabetes
At Diabetes UK we want to find better ways to treat the complications of diabetes. This project will help us understand what happens to kidney cells in people with diabetes and what needs to be done to keep these cells healthy. In the future, this work could help to develop new strategies for treating kidney disease.