Loss of integrin linked kinase from mouse hepatocytes in vitro and in vivo results in apoptosis and hepatitis†
Bibliographic record
Abstract
UNLABELLED: Extracellular matrix (ECM) is fundamental for the survival of cells within a tissue. Loss of contact with the surrounding ECM often causes altered cell differentiation or cell death. Hepatocytes cultured without matrix lose patterns of hepatocyte-specific gene expression and characteristic cellular micro-architecture. However, differentiation is restored after the addition of hydrated matrix preparations to dedifferentiated hepatocytes. Integrin-linked kinase (ILK) is an important component of cell-ECM adhesions transmitting integrin signaling to the interior of the cell. ILK has been implicated in many fundamental cellular processes such as differentiation, proliferation, and survival. In this study, we investigated the role of ILK in mouse hepatocytes in vitro as well as in vivo. Depletion of ILK from primary mouse hepatocytes resulted in enhanced apoptosis. This was accompanied by increased caspase 3 activity and a significant decrease in expression of PINCH and alpha-parvin, which, along with ILK, form a stable well-characterized ternary complex at cell-ECM adhesions. The induction of apoptosis caused by ILK depletion could be substantially reversed by simultaneous overexpression of ILK, indicating that apoptosis is indeed a consequence of ILK removal. These results were further corroborated via in vivo data showing that adenoviral delivery of Cre-recombinase in ILK-floxed animals by tail vein injection resulted in acute hepatitis, with a variety of pathological findings including inflammation, fatty change, and apoptosis, abnormal mitoses, hydropic degeneration, and necrosis. CONCLUSION: Our results demonstrate the importance of ILK and integrin signaling for the survival of hepatocytes and the maintenance of normal liver function.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.000 | 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".