Microscopic ‘Shuttles’ Transport Enzyme From Cells to Trigger Onset of Kidney Disease


Source: University of Sheffield

Summary: Researchers in a new study has identified a key culprit in the onset of kidney disease in a major marker for kidney disease development.


Kidney scarring or ‘fibrosis‘ is the primary cause of kidney disease and is triggered by factors including diabetes, autoimmune disease and high blood pressure, regular use of certain medications and prolonged infections. Kidney disease costs the NHS £1.5bn a year and is thought to be getting more common due to increasing levels of obesity and aging societies. There is currently no cure, with treatment either through dialysis or transplant. Researchers from the University of Sheffield in a new study has identified a key culprit in the onset of kidney disease in a major marker for kidney disease development. They discovered nano-sizedshuttles,’ which transport a damaging enzyme outside of the kidney cells in order for it to begin the scarring process on the surface. The study findings were published in the Journal of the American Society of Nephrology.

Kidney Disease Onset

Credit: University of Sheffield

As part of the study, the team investigated how the enzyme Transglutaminase-2 (TG2) – known to be responsible for kidney scarring was transported from the cells to perform its damaging action. They developed a new approach to detect all TG2-associated proteins in simulated conditions of disease. From here, they were able to identify how TG2 left the kidney cells to cross-link proteins like collagen and fibronectin, leading to fibrosis. After these findings were obtained in models of the disease, the team screened the urine of kidney disease patients, which also showed these tiny vesicles carrying TG2. It is hoped that this study could lead to new therapies to try to block the tiny microvesicles – about 100 nanometers in diameter and potentially stop the disease in its tracks.

Director of research operations at Kidney Research UK, Elaine Davies said, “Kidney Failure is life-threatening and caused when the kidneys no longer function normally due to irreversible scarring within its structure. “This biological mechanism research finding is helping us build our understanding about scarring and will help us to find the tipping point where kidney scarring changes, from being reversible to irreversible.”


More Information: Giulia Furini et al, “Proteomic Profiling Reveals the Transglutaminase-2 Externalization Pathway in Kidneys after Unilateral Ureteric Obstruction”, Journal of the American Society of Nephrology (2018). DOI: 10.1681/ASN.2017050479


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