Abstract: TH-PO0390
Circulating β-Amyloid Disrupts Podocyte α3β1 Integrin Adhesion in FSGS
Session Information
- Glomerular Diseases: Genetics to Therapeutics
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Lopez-Alvarenga, Carmen, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Polat, Onur K., The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Beck, Jordan J., The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Koss, Kyle Michael, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Altintas, Mehmet M., The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Reiser, Jochen, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
Background
Focal segmental glomerulosclerosis (FSGS) is a leading cause of end-stage kidney disease (ESKD) and frequently recurs after kidney transplantation due to circulating pathogenic factors. While soluble urokinase-type plasminogen activator receptor (suPAR) promotes podocyte injury through αVβ3 integrin activation, mechanisms disrupting the adhesion via integrin α3β1 remain unclear. In Alzheimer’s disease, Aβ42 interacts with β1 containing integrins, induces cytoskeletal collapse, and promotes cellular toxicity. We hypothesize that circulating Aβ42 targets podocyte α3β1 integrin, destabilizes integrin cytoskeletal adhesion, and amplifies suPAR-mediated injury in FSGS. Our preliminary studies identified amyloid oligomers in FSGS plasma and demonstrated that amyloid fibers are present in FSGS organoid models, Aβ42 binds α3β1 and promotes amyloid formation in silico and in vitro, and Aβ42 colocalizes with α3β1 and induces injury in cultured human podocytes.
Methods
Differentiated human podocytes are treated with Aβ42 ± suPAR. Injury will be assessed by phalloidin staining, cleaved caspase-3, pFAK, pSrc, Thioflavin-T fluorescence, and transmission electron microscopy (TEM). Rescue studies will include heparan sulfate, integrin β1/β3 blocking antibodies, and uPAR neutralizing antibodies. Integrin dependence will be tested using integrin β1 (ITGB1) and β3 (ITGB3) gene knockdowns. Confocal imaging with biotin-labeled Aβ42 will be used to assess membrane co-localization with integrins, while recombinant integrin capture assays and proteomics will be used to identify amyloid-integrin complexes in FSGS plasma. Inflammatory amplification will be examined using conditioned media and macrophage co-culture systems.
Results
Preliminary studies demonstrate that Aβ42 promotes integrin-dependent FAK/Src activation, cytoskeletal disruption, and podocyte injury. We predict that these effects will be further exacerbated by suPAR and inflammatory signaling. These studies will establish a mechanistic link between circulating amyloid, integrin dysfunction, and podocyte injury in FSGS, identifying amyloid-integrin interactions as a potential therapeutic target.
Conclusion
These studies identify β-amyloid–integrin interactions as a novel mechanism of podocyte injury in FSGS and a potential therapeutic target.
Funding
- NIDDK Support