SMAD3-dependent and -independent pathways in glomerular injury associated with experimental glomerulonephritis
Bibliographic record
Abstract
Glomerulonephritis (GN) is a common cause of end-stage kidney disease and is characterized by glomerular inflammation, hematuria, proteinuria, and progressive renal dysfunction. Transforming growth factor (TGF)-β is involved in glomerulosclerosis and interstitial fibrosis. TGF-β activates multiple signaling pathways, including the canonical SMAD pathway. We evaluated the role of SMAD signaling in renal injury and proteinuria in a murine model of GN. SMAD3+/+ or SMAD3−/− mice received anti-glomerular basement membrane antibodies to induce GN. We confirmed previous reports that demonstrated that SMAD3 is an important mediator of glomerulosclerosis and renal interstitial fibrosis. Proteinuria was highly SMAD3 dependent. We found differential effects of SMAD3 deletion on podocytes and glomerular endothelial cells. GN led to podocyte injury, including foot process effacement and loss of podocyte-specific markers. Interestingly, these changes were not SMAD3 dependent. Furthermore, there were significant changes to glomerular endothelial cells, including loss of fenestrations, swelling, and basement membrane reduplication, which were SMAD3 dependent. Despite ongoing markers of podocyte injury in SMAD3−/− mice, proteinuria was transient. Renal injury in the setting of GN involves TGF-β and SMAD3 signaling. Cell populations within the glomerulus respond differently to SMAD3 deletion. Proteinuria correlated more with endothelial cell changes as opposed to podocyte injury in this model.
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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) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".