TSPO Deletion and Antagonism Reduce Kidney Injury and Fibrosis in Mouse Models

A study in the Journal of the American Society of Nephrology investigated whether translocator protein (TSPO), an outer mitochondrial membrane protein, contributes to kidney injury and fibrosis. Researchers used tubule-specific TSPO-knockout mice in unilateral ureteral obstruction and unilateral ischemia-reperfusion injury models, tested the TSPO antagonist PK11195, and examined metabolic responses in mouse proximal tubular cells and a human tubular cell line. Sample sizes were not provided in the supplied text.

TSPO expression was increased in proximal tubules from patients with chronic kidney disease and in both mouse injury models. Tubule-specific deletion and PK11195 treatment mitigated kidney injury, inflammation and fibrosis in mice. Under hypoxic stress, TSPO-deficient mouse tubular cells showed enhanced mitochondrial biogenesis and membrane potential, increased oxidative phosphorylation and ATP production, and reduced glycolysis. The supplied text reports no numerical effect estimates.

Mechanistic experiments showed that TSPO interacted with mitochondrial hexokinase 2 (HK2). TSPO knockdown shifted HK2 to the cytosol, reducing its glycolytic capacity. These findings identify TSPO-associated metabolic dysfunction as a potential therapeutic target, but the intervention evidence is limited to animal and cellular experiments. Increased TSPO expression in patient tissue does not establish that TSPO inhibition would improve clinical kidney outcomes.