Hepatic Apoptosis Postburn Is Mediated by C-Jun N-Terminal Kinase 2
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Bibliographic record
Abstract
The trauma of a severe burn injury induces a hypermetabolic response that increases morbidity and mortality. Previously, our group showed that insulin resistance after burn injury is associated with endoplasmic reticulum (ER) stress. Evidence suggests that c-Jun N-terminal kinase (JNK) 2 may be involved in ER stress-induced apoptosis. Here, we hypothesized that JNK2 contributes to the apoptotic response after burn injury downstream of ER stress. To test this, we compared JNK2 knockout mice (-/-) with wild-type mice after inducing a 30% total body surface area thermal injury. Animals were killed after 1, 3, and 5 days. Inflammatory cytokines in the blood were measured by multiplex analysis. Hepatic ER stress and insulin signaling were assessed by Western blotting, and insulin resistance was measured by a peritoneal glucose tolerance test. Apoptosis in the liver was quantified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. Liver function was quantified by aspartate aminotransferase and alanine aminotransferase activity assays. Endoplasmic reticulum stress increased after burn in both JNK2 and wild-type mice, indicating that JNK2 activation is downstream of ER stress. Knockout of JNK2 did not affect serum inflammatory cytokines; however, the increase in interleukin 6 mRNA expression was prevented in the knockouts. Serum insulin did not significantly increase in the JNK2 group. On the other hand, insulin signaling (PI3K/Akt pathway) and glucose tolerance tests did not improve in JNK2. As expected, apoptosis in the liver increased after burn injury in wild-type mice but not in JNK2. Aspartate aminotransferase/alanine aminotransferase activity revealed that liver function recovered more quickly in JNK2. This study indicates that JNK2 is a central mediator of hepatic apoptosis after a severe burn.
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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 | 0.000 | 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 it