S-Nitrosylation of RhoGAP Myosin9A Is Altered in Advanced Diabetic Kidney Disease

Area of Science:

• Nephrology
• Molecular Biology
• Diabetology

Background:

• Diabetic kidney disease (DKD) pathogenesis is complex and not fully understood.
• Myo9A, a Rho-GAP protein, is a novel podocyte protein implicated in FSGS.
• Previous studies suggest Myo9A plays a role in DKD.

Purpose of the Study:

• To investigate the effect of a diabetic environment on Myo9A expression and S-nitrosylation.
• To explore the functional consequences of altered Myo9A in podocytes.
• To determine the role of nitric oxide (NO) availability in regulating Myo9A modifications.

Main Methods:

• Studied Myo9A expression and S-nitrosylation in diabetic mouse models and high-glucose treated podocytes.
• Utilized qPCR, immunoblot, immunocytochemistry, proximity ligation assay, and biotin switch assays.
• Assessed podocyte migration and RhoA activity.

Main Results:

• Diabetic conditions significantly decreased glomerular Myo9A expression and S-nitrosylation (SNO-Myo9A) in vivo.
• High glucose reduced Myo9A expression and SNO-Myo9A in podocytes, impairing migration.
• NO donor treatment restored Myo9A function; high glucose also altered SNO-RhoA and SNO-actin.

Conclusions:

• High glucose-induced reduction in Myo9A and SNO-Myo9A is NO-dependent.
• Dysregulation of SNO-Myo9A, SNO-RhoA, and SNO-actin may contribute to advanced DKD.
• Targeting these NO-dependent modifications could offer a therapeutic strategy for DKD.