Abstract

Background: To respond and adapt to their environment cells of the kidney exchange information amongst themselves through transfer of adenosine triphosphate (ATP). communication occurs via membrane bound channels composed of small proteins called connexions. Changes in connexin expression are implicated in progression of several diseases including diabetes. We have examined connexion-mediated ATP release in cells of the diabetic kidney.
Methods: Using model human cells that line the small tubes of the early kidney we used state-of-the-art imaging technologies to compare connexin expression to cell-to-cell communication and function in response to a transforming growth factor associated with high glucose.
Results: Transforming growth factor decreases connexin expression. The pro-fibrotic factor also reduces cell-cell stickiness. As tethering between cells decreases, they are no longer able to communicate directly through connexion-mediated channels. We used novel sensors to measure ATP release from the pores formed as a result of connexin detachment (i.e. semi-channels). Along with dye uptake experiments, these studies confirm a compensatory increase in semi-channel activity.
Conclusion: In disease, cells can alter the way they communicate in an attempt to maintain function. By understanding the language used we identify connexins as a potential therapeutic target in the treatment of diabetic kidney disease.
Acknowledgements: The authors are indebted to Diabetes UK, the European Foundation for the Study of Diabetes (EFSD) and the Diabetes Research & Wellness Foundation (DRWF) for their continued support. Work on urological cell-cell interactions has been partially supported by Rosetree grant A385.