Researchers at Stony Brook University have identified the Glucose Transporter 1 (Glut1) protein as a potential therapeutic target for kidney disease. The study, led by Partha Biswas from the Renaissance School of Medicine at Stony Brook University, focused on antibody-mediated glomerulonephritis (AGN), a severe form of chronic kidney disease (CKD).
According to the Centers for Disease Control and Prevention, CKD affects about one in seven Americans, or approximately 35.5 million people. AGN occurs when the immune system produces antibodies that attack the basement membrane of the kidney's filtering units, leading to inflammation, tissue injury, and eventual kidney failure.
The research team used a mouse model to observe how inflammation affects immune cells in the kidney, particularly neutrophils. "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 Biswas.
Their findings showed that neutrophils increase Glut1 expression and function in diseased kidneys. Glut1 is responsible for transporting glucose into cells and plays an important role in preventing damage by facilitating glucose reabsorption outside the kidney.
After confirming higher Glut1 expression during disease progression, researchers demonstrated that Glut1 activity in inflammatory cells is necessary for advancing AGN pathology. This process leads to increased inflammation and tissue damage early in the disease.
"Essentially, we uncovered a previously unrecognized mechanism in the AGN disease process," Biswas said. "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 study also reported: "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."
Biswas added that these results reveal a key role for 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 grants provided by the National Institutes of Health.