Knockdown of thioredoxin interacting protein attenuates high glucose-induced apoptosis and activation of ASK1 in mouse mesangial cells.

Mesangial cell apoptosis contributes to the pathogenesis of diabetic nephropathy. Here we show that thioredoxin interacting protein (TXNIP) is involved in high glucose (HG)-induced mouse mesangial cell (MMC) apoptosis. HG induced activation of apoptosis signal regulating kinase-1 (ASK1) in a time-dependent manner in MMCs. Treatment with antioxidant, tempol, or knockdown of TXNIP in MMCs reduced HG-mediated apoptosis, expression of cleaved caspase-3, Bax/Bcl-2 ratio and activation of ASK1. These data suggest that knockdown of TXNIP prevented HG-induced cell apoptosis and activation of ASK1 may be via reduction of oxidative stress in MMCs.