Nuclear receptor 4A1 (NR4A1) silencing protects hepatocyte against hypoxia-reperfusion injury <i>in vitro</i> by activating liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) signaling
Bibliographic record
Abstract
The nuclear receptor 4A1 (NR4A1) is widely involved in the regulation of cell survival and is related to ischemic injury in several organs. This research examined the emerging role and mechanism of NR4A1 in hepatocyte ischemia-reperfusion injury (IRI). BRL-3A cells were subjected to hypoxia-reperfusion (H/R) to simulate an IRI model in vitro. The expression of NR4A1 and liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) pathway-related proteins (LKB1, AMPK, and ACC) was detected by western blotting or RT-qPCR under H/R condition after NR4A1 overexpression or silencing. Then, radicicol, an inhibitor of LKB1 pathway, was used to determine the role of NR4A1 in hepatocyte H/R injury by regulating LKB1. Under the help of CCK-8 assay, cell viability was assessed. The levels of ROS, MDA, and SOD were determined with corresponding kits to evaluate oxidative stress. Additionally, RT-qPCR was employed to analyze the releases of the inflammatory factors. Flow cytometry was applied to estimate the apoptosis and its related proteins, and autophagy-associated proteins were assayed by western blotting. Results indicated that NR4A1 was highly expressed, while proteins in LKB1/AMPK signaling was downregulated in BRL-3A cells exposed to H/R. The activation of LKB1/AMPK pathway could be negatively regulated by NR4A1. Moreover, NR4A1 depletion conspicuously promoted cell viability, inhibited oxidative stress as well as inflammation, and induced apoptosis and autophagy in H/R-stimulated BRL-3A cells, which were reversed after radicicol intervention. Collectively, NR4A1/LKB1/AMPK axis is a new protective pathway involved in hepatocyte IRI, shedding new insights into the improvement of hepatocyte IRI.
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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) | 0.001 | 0.001 |
| 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) | 0.004 | 0.001 |
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".