A scientist from the University of Lincoln has won a prestigious funding award from the national Physiological Society to launch new research examining cell-to-cell communication in the diabetic kidney.
Dr Claire Hills from Lincoln’s School of Life Sciences will explore the underlying mechanisms which contribute to altered cell communications and loss of function in the kidneys of people with diabetes.
“Our kidneys are complex organs, tasked with multiple functions including filtering of our blood, the removal of waste products, and regulation of blood pressure and hormone synthesis,” Dr Hills explained. “To work appropriately and perform these tasks efficiently cells in the kidney need to talk to each other and their surrounding environment, adapting in times of stress and responding to any detrimental changes. This cell-to-cell communication is made possible via pores or channels found in the cell membranes. The pores are composed of proteins called connexins, whose altered expression and function has been linked to the development and progression of several secondary complications of diabetes. Evidence that connexin expression is linked to renal damage has led to suggestions about possible new therapeutic targets in the treatment of diabetic nephropathy, and this is what our new research will explore.”
Diabetic nephropathy is a progressive kidney disease caused by damage to the capillaries in the kidney. One of the complications caused by this disease is renal fibrosis (the formation of excess connective tissue during the body’s repair process). Dr Hill’s work – the latest study in an extensive portfolio of diabetes research at the University of Lincoln – will aim to develop an understanding of what exactly happens to cells during this process, and in turn identify future therapeutic targets for alleviating renal fibrosis.
Dr Hills said: “Diabetic nephropathy represents the leading cause of End Stage Renal Disease and accounts for almost a quarter of those entering the kidney transplantation programme. In diabetes, kidney cells are exposed to high levels of glucose and must respond accordingly to ensure that function is maintained. To do so, cells must communicate with each other and their surrounding environment.
“Our current research examines how high levels of glucose and modification of a cells surroundings can alter the ability with which cells talk to each other and respond to incoming ‘danger’ signals from their environment. Understanding the mechanisms by which glucose drives altered cell behaviour is essential in establishing novel therapeutic strategies for the prevention of the disease.”
Current treatments focus on regulating both blood glucose and blood pressure to slow disease progression, however many patients still develop kidney failure in the face of good glycemic control. A deeper understanding of the basic mechanisms that prevent kidney cells from functioning correctly is therefore needed to develop new treatments and preventative measures.
Using biopsy material from the kidneys of patients both with and without diabetic nephropathy, Dr Hills’ preliminary data suggests that patients with diabetic kidney disease exhibit elevated levels of two key connexins. She will now work with a collaborative team of clinicians and scientists to better understand how these connexins represent potential therapeutic targets for the treatment of diabetic nephropathy.
Dr Hills’ study, entitled United we stand, divided we fall: Glucose, TGF-beta and connexin mediated cell-communication in the diabetic kidney, is one of 10 UK projects selected by the Physiological Society to receive funding from its prestigious Research Grant Scheme.
Dr Hills has also previously secured funding from the European Foundation for the Study of Diabetes, Diabetes UK, and DRWF, to research the role of the kidney in diabetes and diabetic nephropathy.