Purinergic Regulation of Diabetic Kidney Disease

Diabetes is the leading cause of renal failure. Inflammation, endothelial dysfunction and microvascular damage are common findings, but causal molecular mechanisms remain poorly understood. We demonstrated previously that renal P2X7 receptor (P2X7R) expression is increased in diabetic patients (DOI: 10.1016/j.ebiom.2017.04.011).

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Diagram of blocking the protein P2X7R from the kidney
This research project explores the impact and role of the protein P2X7R on kidney disease.

In this project we will utilise a preclinical model to investigate whether P2X7R is an essential protein involved in the deleterious vascular dysfunction and damage found in diabetic kidney disease 

Research Methods and Objectives

Inflammation, endothelial dysfunction and microvascular damage is common but causal molecular mechanisms remain poorly understood.
We are performing a series of investigations that aim to: 

  • Determine if genetic deficiency in P2X7R protects kidneys from diabetic damage 

  • Measure diabetic control of macrovascular tone 

  • Investigate cell-cell interactions mediated by purinergic signalling 

This Diabetes UK project grant (17/0005685) is a result of functional data identified in Rob Menzies’ BHF Fellowship (FS/15/61/31626) and previous collaborative work with UCL/Imperial/AstraZeneca published in new Lancet/CellPress open access journal EBIOMED (DOI: 10.1016/j.ebiom.2017.04.011) and covered by the press etc (http://www.bbc.co.uk/news/uk-scotland-edinburgh-east-fife-39642235

Principal Investigator, Co-Investigators, Other researchers

Principal Investigator: Rob Menzies 

Co-Investigators: John Mullins & Matt Bailey