Trehalose alleviates nephropathy in focal segmental glomerulosclerosis via the upregulation of the WT-1/EZH2 pathway
Bibliographic record
Abstract
Introduction: Focal segmental glomerulosclerosis (FSGS) is a serious disease that culminates in kidney failure. Today, FSGS is diagnosed histologically as a progressive scarring of the glomeruli due to gradual loss or damage of the podocyte layer, making it one of the main targets of FSGS therapeutic approaches. However, given that podocytes are terminally differentiated, post mitotic epithelial cells with limited proliferative capacity, they are considered one of the most vulnerable components of the glomeruli. Aim and Methods: We herein investigated the effect of trehalose, a naturally occurring sugar with low toxicity and high stability, on kidney function using a murine model of adriamycin-induced nephropathy. Results: Based on our data, trehalose administration improved proteinuria in mice with FSGS compared to those without FSGS induction (24 h urine protein of 0.30±0.06 versus 0.55±0.08, p-value<0.05, and urine protein to creatinine ratio of 0.78±0.25 versus 1.56±0.17, p-value<0.05, respectively this is accompanied by reduced fibrosis and podocyte damage. Significant reduction in collagen deposition in glomeruli observed in mice treated with trehalose, P-value<0.01 and significant reduction in glomerular basement membrane thickness, P-value<0.001. Moreover, trehalose intake is associated with higher mature podocyte markers at gene and protein expression levels, Nphs1, Nphs2 and Synpo. These favorable effects seem to be mediated mainly via increased WT-1/EZH2 signaling, which is a key pathway in maintaining normal podocyte function and growth. These effects were also observed in the downstream signaling pathway with lower expression of Mmp-7 and Catenin b1 gene expression (p-value<0.05 and <0.01, respectively). Conclusion: Our findings suggest that trehalose could be a promising therapeutic agent for FSGS, nevertheless, more studies are necessary to confirm our findings and evaluate trehalose efficacy in clinical settings.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".