Researchers at Duke-NUS School of Medicine have identified a gene that plays a key role in regulating the energy supply to cells that causes kidney failure. Their discovery is American Society of Nephrology Journalhighlights new approaches to developing treatments and drugs to halt the progression of chronic kidney disease (CKD).

CKD is a global health concern, leading to high mortality rates worldwide. As kidney disease progresses, kidney tissue becomes fibrotic, causing permanent scarring and irreversible organ damage. This condition often leads to end-stage renal disease, and current treatment options are very limited.

“Our study focused on myofibroblasts, a type of kidney cell that is central to scarring of kidney tissue in fibrosis,” said Jack Bemoaras, co-senior author of the new study. the professor said. “By investigating the relationship between the metabolic activity of these cells and disease progression, we have discovered that by modulating the energy supply to myofibroblasts, we may be able to control their function and prevent kidney fibrosis. I found out something.”

The research team, led by Associate Professor Enrico Petretto, analyzed more than 130 biopsy samples taken from patients in China and Italy. Their findings revealed that the presence of the WWP2 gene in myofibroblasts was associated with the progression of renal fibrosis. This gene is important in regulating mitochondria, also known as the cell’s power plants, because they produce the energy needed for cell function.

“In our preclinical model of CKD, we found that high levels of WWP2 rewire cellular metabolism and contribute to fibrosis progression,” said Dr. Chen Huimei, lead author of the paper. . “On the other hand, WWP2 deficiency accelerates renal cell metabolism, slows scar formation, and reduces the severity of renal dysfunction and fibrosis.”

The image panels show that the presence of WWP2 increases fibrotic tissue (left), whereas WWP2 deficiency decreases fibrosis (right). Image credit: Duke-NUS Medical School.

In previous research, the researchers found that WWP2 controls scarring in heart disease. Targeting a patient’s genes may be able to stop the formation of excess scar tissue and slow the progression to heart failure.

“Through our research, we identified WWP2 as a new potential target for drug development to halt the progression of fibrosis in several diseases,” said Dr. Petrett. “This is especially true for CKD, which can progress to kidney failure and is fatal if untreated. paves the way for the design of new and promising treatments.”

Professor Patrick Tan, Duke University’s senior vice president for research, said the study “not only uncovers the genetic mechanisms underlying kidney disease, but also opens up new avenues for therapeutic intervention and supports hundreds of patients around the world. This will give hope to 10,000 CKD patients.” . Researchers are currently in talks with venture capitalists to develop WWP2 inhibitors to treat heart and kidney disease.

Top image credit: iStock.com/Mohammed Haneefa Nizamudeen