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Abstract: FR-PO751

The Actin Cytoskeleton of Injured Podocytes Transforms from a Disorganized Meshwork into Organized Contractile Sarcomere-Like Structures

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

  • Puapatanakul, Pongpratch, Washington University in St Louis School of Medicine, St Louis, Missouri, United States
  • Langner, Ewa, Washington University in St Louis School of Medicine, St Louis, Missouri, United States
  • Qu, Chengqing, Washington University in St Louis, St Louis, Missouri, United States
  • Jiang, Shumeng, Washington University in St Louis, St Louis, Missouri, United States
  • Mahjoub, Moe, Washington University in St Louis School of Medicine, St Louis, Missouri, United States
  • Genin, Guy M., Washington University in St Louis, St Louis, Missouri, United States
  • Miner, Jeffrey H., Washington University in St Louis School of Medicine, St Louis, Missouri, United States
  • Suleiman, Hani, Washington University in St Louis School of Medicine, St Louis, Missouri, United States
Background

Podocytes develop synaptopodin (Synpo)-myosin IIA (MyoIIA)-positive sarcomere-like structures (SLSs) in proteinuric kidney diseases. SLSs are mechanosensitive and may prevent detachment and contribute to recovery. To better understand SLSs biology, we investigated their development in vivo at different stages of injury.

Methods

The Adriamycin nephropathy mouse model was used to portray ongoing podocyte injury. Kidneys were collected at 3, 5, 7, 9, and 14 days post-Adriamycin injection. We combined Ultrastructural Expansion Microscopy and high-resolution confocal imaging to visualize podocyte foot processes (FPs) and SLSs. The extent of SLSs was evaluated by the percentage of SLS area per total FP area.

Results

Albuminuria was evident as early as day 2 and became pronounced by days 5-7. By light microscopy, glomeruli appeared normal on day 5, but segmental sclerosis was observed on days 9 and 14. SLSs were observed focally and segmentally starting from day 3. SLS area percentage increased over time, reaching nearly 100% by day 9. A progression of three Synpo and MyoIIA patterns in SLSs was observed (Fig.1A-C). Pattern 1: Synpo occupying most of the FP space with a few areas infiltrated by MyoIIA. Pattern 2: Alternating, disorganized Synpo-MyoIIA, with Synpo-positive bundles retained at the FP periphery. Pattern 3: Periodic, well-organized Synpo-MyoIIA striations, perpendicular to the original longitudinal axis, with peripheral Synpo bundles gone. Pattern 1 was dominant on day 3, while Pattern 3 represented over 80% of SLSs from day 7 onward. Pattern 2 became dominant on day 5, then yielded to Pattern 3 (Fig.1D).

Conclusion

Correlation between SLS patterns and timing after injury suggests that SLSs undergo stages of development from less organized actomyosin to well-organized sarcomeric patterns that exert longitudinal contractile forces. Further clinical correlation of SLS patterns may aid in predicting the fate of podocytes and disease prognosis.

Funding

  • NIDDK Support