Researchers at Stony Brook University have identified the Glucose Transporter 1 (Glut1) protein as a possible therapeutic target for kidney disease. The study, led by Partha Biswas of the Renaissance School of Medicine at Stony Brook University, was published in the Journal of Clinical Investigation Insight.
Chronic kidney disease (CKD) affects an estimated 35.5 million Americans, according to data from the Centers for Disease Control and Prevention. One severe form of CKD is antibody-mediated glomerulonephritis (AGN), where antibodies attack parts of the kidneys, causing inflammation and tissue damage that can lead to kidney failure.
The research team used a mouse model to examine how inflammation develops in AGN. They focused on neutrophils, immune cells that respond during this process.
“While metabolic reprogramming has already transformed treatment strategies for cancer and autoimmune diseases, it has not been explored as a therapeutic avenue for neutrophils in AGN,” said Dr. Biswas, who is also a professor in the Department of Microbiology and Immunology at Stony Brook.
The study found that neutrophils increased their expression of Glut1 in diseased kidneys. Glut1 helps transport glucose into cells and plays a role in glucose reabsorption outside the kidney, preventing additional damage.
After confirming higher Glut1 expression during disease progression, researchers showed that disabling Glut1 function in inflammatory cells reduced AGN-related pathology, particularly during early stages when inflammation and tissue damage increase.
“Essentially, we uncovered a previously unrecognized mechanism in the AGN disease process,” said Dr. Biswas. “We then found that by selectively disabling Glut1 in neutrophils there is a dramatic reduction in their tissue-damaging effector functions throughout disease progression.”
The authors noted further: “while neutrophil-specific Glut1 ablation diminished the expression of tissue-damaging effector molecules in both early and late stages, renal cytokines’ and chemokines’ production were compromised only in the late stage of disease. Consequently, the Glut1 inhibitor treatment ameliorated renal pathology in AGN mice.”
Dr. Biswas stated that these findings highlight an important pathway involving Glut1 within neutrophils: “This circuit is not only central to disease pathology but also highly targetable and positions neutrophil metabolic prevention as a promising, and previously untapped, therapeutic strategy for AGN and potentially other forms of CKD.”
The research received support from the National Institutes of Health through several grants.