Oncostatin M Receptor Reflects Organ Injury Associated with the Local and Systemic Inflammatory Response
Bibliographic record
Abstract
Introduction: Brain death induces a massive systemic inflammatory response syndrome. Human kidney biopsies taken at time of transplantation show marked inflammation in deceased donor (DD) kidneys compared to living donor (LD) kidneys largely mediated by the Oncostatin M/Oncostatin M Receptor (OSM/OSMR) axis (Am J Transpl, Am J Ren Physiol). In the underlying studies we try to further understand the role of OSM/OSMR in local and distant inflammation and organ injury by using animal models of acute kidney injury and sepsis. Methods: Male C57BL/6 mice (3 mo old, ≥ 3 mice per condition) underwent unilateral renal ischemia-reperfusion (AKI model) or cecal ligation and puncture (sepsis model). Inflammation and injury markers including OSM, OSMR, IL6, IL6R, LIF, LIFR, SERPINA3, NGAL and KIM1 were measured at 24 hours by PCR and ELISA in heart, lung, kidney, liver and blood in addition to histopathology scoring and BUN measurements. Results: Compared to control and sham operated tissue OSMR was consistently up-regulated in the clamped kidneys (local injury) as well as in the organs distant to the local injury (contra-lateral non-clamped kidneys, extra-renal organs exposed to kidney clamping as well as to sepsis). In addition, the increase in OSMR levels correlated with the severity of sepsis induced by varying sizes of cecal puncture holes (p< 0.5) and OSMR levels reflected as well the degree of histological damage and impairment in kidney function. In the distant organs the overall inflammatory response pattern was qualitatively similar between AKI and sepsis for the analyzed gene transcripts as shown for NGAL in figure 1. Distant organ expression patterns were comparable in sepsis and AKI mice (Figure 1). In hearts, kidneys and lungs NGAL increased by 417, 340 and 19 fold in sepsis, compared to 33, 340 and 9 fold in AKI. Baseline expression was consistently higher in the lung for all the inflammation genes, followed by heart and then kidney.[Fig 1]Conclusion: Systemic inflammation induces a highly stereotyped response in distant organs. The degree of associated local and systemic organ injury is reflected by the level of OSMR 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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".