Role and regulation of the proprotein convertase subtilisin/kexin type 9 (PCSK9) in the small intestine
Bibliographic record
Abstract
Proprotein convertase subtilisin kexin type 9 (PCSK9) is playing a central role in the pathogenesis of atherosclerosis. This enzyme reduces cellular uptake of plasma LDL‐cholesterol by promoting LDL receptor degradation in liver through an unknown posttranscriptional mechanism. The current investigation was undertaken to explore the role and regulation of PCSK9 in human enterocytes. To this end, molecular strategieswere devised in the Caco‐2 cell line to determine the importance of PCSK9 in intestinalcholesterol transport and metabolism. Knockdown of PCSK9 caused a decline in the ability of Caco‐2 cells to capture micellar [14C]‐free cholesterol, and resulted in increased activity of HMG‐CoA reductase. To examine the regulation of PCSK9, various effectors were administered to the apical side of Caco‐2 cells for a 24‐h period. Taurocholic acid produced a significant decrease (30%, p<0,01) in PCSK9 gene expression, whereas inflammation agents (LPS, TNF‐α), oxidative stress inducer (iron‐ascorbate), long‐chain fatty acids (DHA, EPA) and glucose showed no effect on mRNA levels. Similarly, insulin did not modify PCSK9 gene expression in the small intestine, in contrast with the findings obtained in rat liver. Together, our data suggest that PCSK9 contributes to intestinal cholesterol homeostasis and a different regulation characterizes the intestine and the liver.
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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 | 0.000 |
| 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".