Abstract: FR-PO0783
GARP/LRRC32 in Podocytes Contributes to the Development of Glomerulosclerosis in Adriamycin-Treated Mice
Session Information
- Glomerular Diseases: Cell Homeostasis and Novel Injury Mechanisms
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Obana, Masanori, Osaka Daigaku, Suita, Osaka Prefecture, Japan
- Yoshitsugu, Yui, Osaka Daigaku, Suita, Osaka Prefecture, Japan
- Sakai, Hibiki, Osaka Daigaku, Suita, Osaka Prefecture, Japan
- Tanaka, Shota, Osaka Daigaku, Suita, Osaka Prefecture, Japan
- Asanuma, Katsuhiko, Chiba Daigaku, Chiba, Chiba Prefecture, Japan
- Okada, Yoshiaki, Osaka Daigaku, Suita, Osaka Prefecture, Japan
- Fujio, Yasushi, Osaka Daigaku, Suita, Osaka Prefecture, Japan
Background
Although podocytes play a pivotal role in glomerulosclerosis, the molecular mechanisms are not fully understood. Previous comprehensive gene expression analysis showed that Glycoprotein A Repetitions Predominant (GARP, also LRRC32), which is involved in the mature transforming growth factor (TGF)-β, is highly expressed in glomeruli. However, the pathophysiological roles of GARP in glomeruli, especially podocytes, are unknown.
Methods
Cultured murine podocytes were treated with adriamycin (ADR), and the GARP expression was examined using immunofluorescence and western blotting. Podocyte-specific GARP knockout (GARP cKO) mice were also treated with ADR, and serum creatinine and urinary albumin/creatinine ratio (ACR) were measured. Glomerulosclerosis was evaluated using PAS staining, immunohistochemistry with anti-PDGFRβ antibody, and electron microscopy. The glomeruli were isolated from GARP cKO mice.
Results
ADR treatment upregulated GARP expression in cultured murine podocytes and murine glomeruli. Although serum creatinine and ACR were unaltered in GARP cKO mice compared with control mice 2 weeks after ADR treatment, lower glomerulosclerosis and suppression of glomerular basement membrane thickening were observed in GARP cKO mice (Glomerular sclerosis index: control; 3.38±0.25, cKO; 2.65±0.40). The protein expression of PDGFRβ was downregulated in the glomeruli of ADR-treated GARP cKO mice (% of PDGFRβ-positive area/glomerulus: control; 3.64±0.58, cKO; 1.68±0.36). Consistently, TGF-β signaling-associated proteins, such as p-Smad2, α-smooth muscle actin, and PDGFRβ, were suppressed in the glomeruli isolated from GARP cKO mice.
Conclusion
GARP in podocytes contributes to glomerulosclerosis in ADR-treated mice, providing valuable insights into the pathogenesis of glomerular diseases.