Abstract: TH-PO0835
Src-Dependent Caveolae-Mediated Albumin Endocytosis Through Glomerular Endothelial and Epithelial Cells Drives Albuminuria and Is Suppressed by Genistein in Diabetic Nephropathy
Session Information
- Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 1900 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Moriyama, Takahito, Tokyo Ika Daigaku, Shinjuku, Tokyo, Japan
- Saito, Suguru, Tokyo Ika Daigaku, Shinjuku, Tokyo, Japan
- Kanno, Yoshihiko, Tokyo Ika Daigaku, Shinjuku, Tokyo, Japan
Background
Albuminuria plays a critical role in the progression of glomerulonephritis, and we previously analyzed a novel therapeutic approach to reduce albuminuria by interfering with intracellular trafficking of albumin in glomerular endothelial cells (GECs) and podocytes (Pods) in nephrotic syndrome modeled mice. In this study, by using in vitro studies with GECs and Pods and an in vivo study using streptozotocin induced diabetic nephropathy mice (diabetic mice), we explored its underlying mechanisms about genistein (Gen), a non-steroidal phytoestrogen and potent soy isoflavone, reduces albuminuria.
Methods
GECs and podocytes were treated with 100 or 200 μM Gen and 50 mM glucose for 60 min, followed by albumin exposure for an additional 60 min. Albumin uptake and expression of caveolin-1 (Cav-1) and phosphorylated Src (p-Src) were evaluated by immunofluorescence (IF) and western blotting (WB). Using the same protocol, albumin concentrations on the insides and outsides of transwell plates with fully confluent GECs or Pods were analyzed. In vivo effects were examined by the p-Src and caveolin-1 (Cav-1) expression in glomeruli and amount of albuminuria in diabetic mice treated with Gen for 14 days.
Results
High glucose significantly increased albumin uptake and expression of p-Src and Cav-1 in both GECs and podocytes, whereas Gen significantly suppressed these effects in a dose-dependent manner by WB (p<0.05) and IF (p<0.05). Albumin transcytosis across GECs and Pods cultured on transwell plates was increased by high glucose (p<0.05) and significantly reduced by Gen (p<0.01). In diabetic mice, Gen significantly reduced albuminuria (0.28 to 0.05, p=0.02) without affecting body weight or blood glucose levels, whereas vehicle treatment had no significant effect (0.21 to 0.14, p=0.37). Glomerular p-Src and Cav-1 expression were also significantly decreased by Gen treatment (p<0.05).
Conclusion
Genistein suppresses Src-dependent caveolae-mediated albumin endocytosis in glomerular endothelial cells and podocytes, resulting in reduced albuminuria in diabetic mice. These findings identify a Src kinase as a pivotal role in intracellular albumin trafficking through cavelae in diabetic nephropathy.