Effect of GDF15 on acetaminophen (APAP)-induced liver injury in mice
Bibliographic record
Abstract
Abstract Acetaminophen (APAP)-induced liver injury (AILI) has been recognized as a pivotal contributor to drug-induced liver failure in western countries, but its molecular mechanism remains poorly understood. After data mining using the Gene Expression Omnibus (GEO) database, we found that the gene expression of growth differentiation factor 15 (GDF15) increased significantly after APAP-induced hepatotoxicity in mouse liver. However, the precise role of GDF15 in AILI has yet to be clarified. To deal with this question, we first examined the temporal gene expression pattern of GDF15 after APAP treatment. Next, overexpression of hepatic GDF15 using adeno-associated virus serotype 8 (AAV8) was employed to investigate the role of GDF15 in AILI. In addition, therapeutic administration of recombinant human GDF15 (rhGDF15) was conducted to probe its curative effect after APAP overdose. We observed that protein expression of GDF15 was significantly increased after APAP overdose. However, there were no significant differences in AILI-related outcomes after overexpression or supplementation of GDF15. The contents of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), morphological feature of liver, the level of reduced form of glutathione (GSH), the activation of c-Jun-N-terminal kinase (JNK), the expression of genes relevant to oxidative stress and cell proliferation were not remarkably changed between AAV8-GFP and AAV8-Gdf15 groups. Although the liver injury was not improved by rhGDF15 administration, the gene expression levels of glutamate-cysteine ligase modifier subunit (Gclm) and glutamate-cysteine ligase catalytic subunit (Gclc) which function downstream of Nrf2 signaling pathway were significantly increased. Altogether, despite a noticeable elevated expression after APAP overdose, GDF15 overexpression or supplementation exerted no significant ameliorative effect on AILI. Further mechanism and consequence of Gclm and Gclc elevation by GDF15 remains to be elucidated.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| 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".