2019 CCS research highlights: Department of Diabetes

L-R: All the RAGE: L-R Ms Alex Dimiropoulos, Dr Raelene Pickering,
Dr Chris Tikellis, Dr Carlos Rosado, Professor Merlin Thomas,
Ms Maria Alejandra Zuniga-Gutierrez

Monash University's Central Clinical School is at the cutting edge of medical research in national and international arenas. We are publishing a series of our research highlights from across 2019.

 In this article we feature a highlight from the Department of Diabetes.

Scientists harness RAGE for good 


The Receptor for Advanced Glycation End-products (RAGE) is an important player in many diseases, from atherosclerosis and diabetes to cancer and neurodegenerative disease. In each of these conditions, RAGE kindles inflammation, cell proliferation and death. But there has been no way to block its effects.

Monash researchers led by Professor Merlin Thomas from the Department of Diabetes have discovered a possible way of doing this.

In an article in the Journal of Clinical Investigation (JCI), the researchers describe a new pathway by which RAGE can be transactivated by the angiotensin receptor with which it forms a complex. Angiotensin is a peptide hormone that causes constriction of blood vessels and an increase in blood pressure. But in the presence of RAGE it also triggers inflammation.

This pathway likely represents the major way that RAGE is activated, Professor Thomas said.

“Mice lacking RAGE are protected against atherosclerosis associated with diabetes. So we gave them back just the inside part of RAGE and this was enough to restore their sensitivity to diabetic complications," he said. “This proves it’s really the inside we should be targeting.”

The researchers developed a selective inhibitor of the inner tail of RAGE, which was able to block inflammation and atherosclerosis. More therapeutics are being developed based on these novel discoveries that may be applicable across a broad range of conditions in which RAGE has been implicated.

See more detail in our feature story.