Mechanoprotection by Polycystins Against Apoptosis is Mediated Through the Opening of Stretch‐Activated K2P Channels
Bibliographic record
Abstract
How cells sense and adapt to mechanical stress remains poorly understood. The TREK two‐pore K + (K2P) subunits underlie the stretch‐activated K + ‐selective channels (SAKs). Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in either PKD1 or PKD2 genes, encoding the polycystins PC1 and PC2. Cystogenesis results mainly from an increase in tubular epithelial cells proliferation. Nevertheless, how a few cysts (typically less than 1% of the nephrons) may impair the function of the majority (99%) of non‐cystic nephrons, ultimately leading to kidney failure, is still an unresolved question. An increase in intra‐renal mechanical stress leading to tubular cells apoptosis and formation of atubular nephrons is a proposed mechanism. In our study, Pkd1 knock out or expression of a PC2 pathogenic mutant enhances tubular cells apoptosis induced by mechanical stress. We show that polycystins protect renal epithelial cells against mechanical stress and this effect is mediated through the opening of SAKs. We establish for the first time, both in vitro and in vivo, a functional relationship between mechanotransduction and mechanoprotection (Peyronnet et al. 2012 Cell Rep 1(3): 241–250). Funding: ANR, FRM, EEC, FRHTA, FRC, Human Frontier, Fondation de France, AFM, AIRG, Région PACA, SFHTA.
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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) | 0.001 | 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".