By investigating the link between the metabolic activities of these cells and the progression of the disease, we discovered that by regulating energy supply to myofibroblasts, we can control their function and potentially halt kidney fibrosis,” said Associate Professor Jacques Behmoaras from the Cardiovascular and Metabolic Disorders Programme at Duke-NUS, who co-led this study.   

WWP2, it turns out, hijacks the cells’ powerhouses, or mitochondria, diverting the cells to release collagen instead of energy—energy that powers healthy cell growth and regeneration. 

“In our pre-clinical models of chronic kidney disease, we discovered that a higher level of WWP2 ‘re-wires’ the cell’s metabolism, contributing to the advancement of fibrosis. On the other hand, a lack of WWP2 boosts metabolism in renal cells and slows down scar formation, reducing the severity of kidney dysfunction and fibrosis,” said Dr Chen Huimei, Principal Research Scientist with the Programme and first author of the study, which was published recently in the Journal of the American Society of Nephrology.

This latest project builds on previous work, in which the team showed that WWP2 controls scarring in heart disease when it is active in a type of immune cell called macrophage. Targeting the gene in patients in the early stages of heart failure could halt the formation of excessive scar tissue and delay the progression of disease.

“Through our studies, we have shown that WWP2 is a new potential target for the development of drugs to halt the progression of fibrosis in several diseases. This is especially so for chronic kidney disease, which can progress to renal failure and is fatal without treatment. Our findings pave the way for the design of new and promising therapies for such illnesses that would otherwise have limited treatment options,” said systems geneticist Associate Professor Enrico Petretto from the same programme who co-led the study with Behmoaras.