Research Progress on the Mechanism of TXNIP Protein in Diabetic Complications and Related Markers

Abstract

TXNIP (Thioredoxin-interacting protein), a key manager of oxidant stress, plays an important role in the pathomechanism of diabetic complications. This review systematically elucidates how TXNIP contributes to diabetic kidney disease (DKD), retinopathy (DR), and peripheral neuropathy through mechanisms involving NLRP3 inflammasome activation and epigenetic modifications. Under high glucose conditions, TXNIP upregulation dissociates from thioredoxin (TRX), binds to NLRP3 via its leucine-rich repeat domain. In DKD, TXNIP overexpression exacerbates renal oxidative stress and mesangial cell apoptosis, while its deficiency preserves β-cell survival and function via AKT/Bcl-xL signaling. In DR, TXNIP inhibition improves angiogenesis and blood-retinal barrier integrity by suppressing NLRP3-mediated inflammation in endothelial cells. Additionally, TXNIP’s role in neurodegenerative diseases are linked to glutamate neurotoxicity and NLRP3 activation. Therapeutic strategies include TIX100, a small-molecule inhibitor targeting TXNIP transcription, which effectively ameliorates diabetes in animal models, and moderate NO levels, which protect retinal cells by directly inhibiting TXNIP/NLRP3 signaling. Future research is needed to optimize TXNIP-based therapies for diabetes and metabolic diseases, highlighting its potential as a diagnostic marker and therapeutic target.