Abstract: TH-PO0309
Intermediate Filaments Regulate Major Process-Like Network and Mechanical Stability in Primary Podocytes
Session Information
- Glomerular Diseases: Cell Biology
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
- Jiang, Shumeng, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Miner, Jeffrey H., Washington University in St Louis, St. Louis, Missouri, United States
- Genin, Guy M., Washington University in St Louis, St. Louis, Missouri, United States
- Suleiman, Hani, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
Background
Cytoplasmic intermediate filaments, including vimentin and nestin, are highly expressed in healthy podocytes and mainly localize to podocyte major processes within the glomerulus. Although they are generally thought to provide structural support, their distinct mechanical properties and specific roles in maintaining podocyte architecture remain unclear. A major limitation in studying these process networks has been the lack of a reliable in vitro system.
Methods
Using a newly established primary mouse podocyte 2D culture system, protrusions resembling major processes network could be observed in vitro, enabling our investigation into the mechanical properties and the roles of different intermediate filament proteins.
Results
Similar to podocytes’ major process, our 2D-cultured primary podocytes show vimentin-rich filaments surrounding thick aligned microtubules networks, with podocalyxin wrapping around the surfaces of those extensions. Disruption of either intermediate filaments or microtubules caused network disassembly, suggesting that both are required for structural integrity.
Among podocyte-expressed cytoplasmic intermediate filaments, vimentin appeared to serve as a core component for major process regeneration. In contrast, nestin was not required during the initial steps of regeneration. Desmin, which is upregulated in injured podocytes, marked a dedifferentiated phenotype and compromised the ability of podocytes to re-establish major process networks. These distinct functions may reflect differences in their mechanical properties. When mechanical disruption was applied to podocytes, nestin appeared to act as a buffer that better preserved process network stability.
Conclusion
We established a 2D primary podocyte culture system that enables regeneration of major process-like networks, providing a useful platform for future studies of podocyte major processes. Our findings identify cytoplasmic intermediate filaments, particularly vimentin, as key regulators of network regeneration. Together with microtubules, vimentin-rich networks may provide a structural framework that supports podocyte architecture and recovery after injury, while nestin may enhance network stability under mechanical disturbance.
Funding
- NIDDK Support