Catalase prevents maternal diabetes-induced perinatal programming via the Nrf2-HO-1 defense system

Area of Science:

• Nephrology
• Developmental Biology
• Biochemistry

Background:

• Maternal diabetes can program offspring for hypertension and kidney disease.
• Reactive oxygen species (ROS) play a role in this programming.
• Catalase (CAT) is an antioxidant enzyme that reduces ROS.

Purpose of the Study:

• To investigate if catalase overexpression in renal proximal tubular cells (RPTCs) can prevent hypertension and kidney disease in offspring of diabetic dams.
• To explore the underlying molecular mechanisms, including the Nrf2-HO-1 pathway.

Main Methods:

• Used transgenic mouse models (Hoxb7-GFP-Tg and Hoxb7/CAT-GFP-Tg) with and without maternal diabetes.
• Assessed offspring from prenatal to adult stages for nephrogenesis, blood pressure, renal function, kidney injury, and ROS generation.
• Analyzed gene expression of TGF-β1, Nrf2, and HO-1 in vitro and in vivo.

Main Results:

• Offspring of diabetic dams showed renal dysmorphogenesis, hypertension, hyperfiltration, kidney injury, and increased ROS.
• Catalase overexpression in RPTCs ameliorated these adverse effects in offspring of diabetic dams.
• Catalase promoted Nrf2 nuclear translocation and HO-1 gene expression, activating the Nrf2-HO-1 defense system.

Conclusions:

• Catalase overexpression in RPTCs prevents maternal diabetes-induced perinatal programming of hypertension and kidney disease in male offspring.
• This protective effect is mediated, in part, by the activation of the Nrf2-HO-1 defense system.
• Targeting catalase may be a therapeutic strategy for preventing diabetes-related developmental complications.