Altered expression, but small contribution, of the histone demethylase KDM6A in obstructive uropathy in mice
Bibliographic record
Abstract
Epigenetic processes have emerged as important modulators of kidney health and disease. Here, we studied the role of KDM6A (a histone demethylase that escapes X-chromosome inactivation) in kidney tubule epithelial cells. We initially observed an increase in tubule cell Kdm6a mRNA in male mice with unilateral ureteral obstruction (UUO). However, tubule cell knockout of KDM6A had relatively minor consequences, characterized by a small reduction in apoptosis, increase in inflammation and downregulation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway. In proximal tubule lineage HK-2 cells, KDM6A knockdown decreased PPARγ coactivator-1α (PGC-1α) protein levels and mRNA levels of the encoding gene, PPARGC1A. Tubule cell Kdm6a mRNA levels were approximately 2-fold higher in female mice than in male mice, both under sham and UUO conditions. However, kidney fibrosis after UUO was similar in both sexes. The findings demonstrate Kdm6a to be a dynamically regulated gene in the kidney tubule, varying in expression levels by sex and in response to injury. Despite the context-dependent variation in Kdm6a expression, knockout of tubule cell KDM6A has subtle (albeit non-negligible) effects in the adult kidney, at least in males.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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".