Nephrin Trafficking in the Mouse Model of Experimental Autoimmune Nephrotic Syndrome
Bibliographic record
Abstract
Background: Nephrin is an essential protein expressed at the slit diaphragm of podocytes and plays a crucial role in maintaining the integrity of the glomerular filtration barrier. We previously developed a novel experimental autoimmune mouse model resembling idiopathic nephrotic syndrome in humans, induced by immunization with Crb2, a slit diaphragm protein that interacts with nephrin. While proper trafficking of nephrin to the podocyte surface is critical for its function, and impaired nephrin turnover contributes to podocyte injury, the mechanisms underlying nephrin trafficking in this model remain unknown. Methods: Cell surface nephrin expression following anti-Crb2 antibody stimulation was studied by biotinylation and western blotting using immortalized human podocytes. Nephrin expression and localization in mouse kidney were evaluated by western blotting and immunofluorescence staining. Markers of endocytosis and autophagy were used to identify the trafficking pathways involved. Results: Cell surface expression of nephrin was significantly reduced following anti-Crb2 antibody stimulation. In Crb2-immunized mouse kidney, nephrin staining intensity decreased, and its reduced expression was confirmed by western blotting. Nephrin showed increased colocalization with the endocytosis markers Rab5 and Rab7, indicating enhanced endocytosis. Furthermore, nephrin colocalized with the autophagy marker LC3. Triple staining for nephrin, LC3 and Rab7 was also increased, suggesting nephrin processing via the amphisomal pathway. Additionally, colocalization of nephrin with the lysosomal marker LAMP1 was increased, indicating lysosomal degradation of nephrin. Conclusion: Nephrin undergoes endocytosis and is degraded via the amphisome-lysosome pathway in the Crb2-induced nephrotic syndrome mouse model, providing new insights into the pathogenesis of podocyte injury in nephrotic syndrome.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".