c-Myc Signalling in the Genetic Mechanism of Polycystic Kidney Disease
Bibliographic record
Abstract
The Myc family of transcription factors regulates major biological processes such as proliferation, stem/progenitor cell pluripotency, metabolism, apoptosis, cell growth and differentiation. The most-studied member c-Myc is essential in embryonic development and cellular homeostasis. Dysregulation of c-Myc protein function is not only associated with malignant transformation and human tumors but is also implicated in autosomal dominant polycystic kidney disease (ADPKD), a human genetic disorder, considered a neoplasia in disguise. Studies from human ADPKD kidneys, caused by mutation in the PKD1 or PKD2 genes, revealed high expression of c-Myc with strong signal detected over cystic tubular epithelium. Consistent with human ADPKD pathogenesis, mouse models produced by dysregulation of Pkd1 and Pkd2 gene dosage show stimulation of renal c-Myc expression. Induced renal c-Myc expression is also observed in several non-orthologous animal models of PKD. Significantly, c-Myc overexpression specifically targeted to renal epithelial cells in transgenic mice closely reproduces human ADPKD. The specific causal effect of c-Myc in PKD was demonstrated by targeting different oncogenes which could not mimic the PKD phenotype. In fact, c-Myc was shown to be a major mediator of renal cystogenesis through various mechanisms and signalling pathways. Most importantly, inhibition of c-Myc in vivo, directly by repressing translation or indirectly with a small-molecule inhibitor, significantly delayed cystogenesis in the mouse. In summary, c-Myc is a central node in the pathogenesis of Pkd1/Pkd2 mouse models and of human ADPKD development and progression.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".