Does Cathepsin B (CTSB) modulate diabetic cardiomyopathy via NLRP3-mediated pyroptosis in mice?
Cathepsin B aggravates diabetic cardiomyopathy by promoting NLRP3-mediated pyroptosis, suggesting it as a potential therapeutic target.
model. CTSB protein level was increased in diabetic cardiomyopathy (DCM) mice heart as well as in cardiomyocytes stimulated with high glucose. CTSB knockout mice showed ameliorated cardiac function, cardiac fibrosis, cardiac inflammation, and pyroptosis level. Oppositely, DCM mice with CTSB transgene showed exacerbated cardiac dysfunction, fibrosis, inflammation, and pyroptosis. We found that CTSB could bind to NLR family pyrin domain containing 3 (NLRP3), thus increasing the activation of the NLRP3/caspase-1 inflammasome pathway. When we used a NLRP3 knockout mice, the deteriorating effect of CTSB overexpression via adeno-associated virus (AAV)9 delivery was abolished. Taken together, CTSB aggravates diabetic cardiomyopathy via promoting NLRP3-mediated pyroptosis.
Liu et al. (Fri,) studied this question.