Abstract: SA-PO707
Autophagic Inhibitor ROC-325 Ameliorates Glomerulosclerosis and Podocyte Injury via Inhibiting Autophagic Flux in Experimental FSGS Mice
Session Information
- Glomerular Diseases: Therapeutic Strategies
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Liang, Xinling, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Zhang, Li, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Li, Jiaying, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Yang, Yan, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Li, Lu-an, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
Background
Podocyte-specific Yes-associated protein (YAP) deletion mice(YAP-KO mice), is considered a new animal model to study the underlying mechanism of FSGS. We sought to determine the therapeutic benefit of ROC-325, a novel small-molecule lysosomal autophagy inhibitor in FSGS model.
Methods
Mass spectrometry were used to profile the downstream pathways in YAP-KO mice. Foot process morphology and autophagy level were detected by transmission electron microscopy. Immunofluorescence measured autophagy level and autophagic flux.
Results
Mass spectrometry showed the processes linked to lysosome dysregulation have been significantly enrich in the YAP-KO mice. The results showed albuminuria, mesangial matrix expansion, and focal segmental glomerulosclerosis in YAP-KO mice were significantly attenuated by ROC-325. Corrugated capsule formation was greatly altered by ROC-325. Furthermore, ROC-325 treatment inhibited the autophagy activaty induced by YAP-KO by inhibiting autophagosome-lysosome fusion, and accumulation of LC3 and p62. Meanwhile, preapplication of ROC-325 in podocyte markedly suppressed autophagic flux.
Conclusion
These results showed that the role of autophagic activity in FSGS and ROC-325 could be a promising agent for the treatment of FSGS.
Funding
- Government Support – Non-U.S.