<scp>NTPDase8</scp> Protects Against Liver Ischemia–Reperfusion Injury in Mice
Bibliographic record
Abstract
ABSTRACT CD39 or NTPDase1 and other nucleoside triphosphate diphosphohydrolases (NTPDases), including NTPDase2, NTPDase3, and NTPDase8, regulate purinergic signaling through tuning the extracellular levels of purine nucleotides and nucleosides. Purinergic signaling regulates liver ischemia–reperfusion (I/R) injury, and CD39 is protective. However, the role of other NTPDases is unknown. In this study, we investigated the role of NTPDase2, NTPDase3, and NTPDase8. Global Entpd2 −/− , Entpd3 −/− , and Entpd8 −/− and control wild type (WT) mice were subjected to liver I/R. In addition, WT and Entpd8 −/− mice underwent global ischemia induced by hemorrhagic shock and resuscitation and injury evaluated. Bone marrow chimeric mice were generated to understand the role of NTPDase expression on hematopoietic cells in regulating liver injury. Although WT, Entpd2 −/− and Entpd3 −/− mice exhibited comparable levels of liver injury following local IR, Entpd8 −/− mice had increased liver injury compared to WT mice. Studies with bone marrow chimeric mice indicated that NTPDase8 on parenchymal liver cells protected against hepatic injury. This was confirmed by single‐nucleus RNAseq showing hepatocytes are the dominant cell type expressing NTPDase8 in the liver. Entpd8 −/− mice after I/R injury were noted to have higher ATP concentrations in the liver and plasma. The P2 receptor antagonist suramin decreased liver injury in Entpd8 −/− mice indicating P2 signaling contributes to liver injury in these mice. Finally, Entpd8 −/− mice had increased liver injury compared to WT mice also after hemorrhagic shock and resuscitation. These findings highlight the differential roles of NTPDase family members in the liver, with parenchymal/hepatocyte expression of NTPDase8 emerging as a critical suppressor of the inflammatory and metabolic responses to hepatic I/R insult, even in the presence of vascular NTPDase1 expression.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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".