FERROPTOSIS AND PYROPTOSIS IN KIDNEY MACROPHAGES AND EPITHELIAL KIDNEY CELLS IS MEDIATED BY A METABOLIC SWITCH TOWARD GLYCOLYSIS IN LUPUS NEPHRITIS
Bibliographic record
Abstract
PT019 / #196 Topic: AS16 - Lupus Nephritis-Pathogenesis POSTER TOUR 04: SLE PATHOGENESIS 24-05-2025 10:00 AM - 10:20 AM Background/Purpose Lupus nephritis (LN) is a type of immune-complex nephritis caused by systemic lupus erythematosus, a chronic autoimmune inflammatory disease frequently identified with a poor prognosis. Macrophages and renal tubular cells play an important role in the pathogenesis of LN. Understanding the mechanisms that lead both types of cells to sustained renal inflammation and development of LN is not well defined and is crucial for developing novel therapeutic strategies. Methods We used rat NRK-52E tubular cells and mice Raw 264.7 macrophages treated with ovalbumin immunocomplexes (OVA-IC) to mimic lupus nephritis injury model in vitro. Experimental groups were: the control group, OVA-IC group, the 2DG (2-desoxi-D-glucose) group, and DFO (deferroxamine) group. Human HK-2 tubular cells and THP-1 monocytes were treated with healthy serum or lupus nephritis serum. After 24 hours of culture, glycolysis and ferroptosis activity assay was analyzed and expression levels related to pyroptosis, ferroptosis, glycolisis, fatty acid oxidation and fibrosis genes were detected by q-PCRS. An in vivo murine model of LN was conducted in CD-1 mice subjected to intraperitoneal administration of pristane. Experimental groups were: sham group and pristane-induced group. Six weeks after, cell sorting was used to isolate renal epithelial and macrophages cells to be analyzed. Results Our results demonstrate that OVA-IC administration promotes glycolysis upregulation and enhances ferroptosis and piroptosis, which were reverted by 2DG and DFO treatment in NRK and RAW cells. In the in vivo mice pristane-induced model, the isolated renal epithelial cells and macrophages from kidneys, showed an increase in the expression of glycolytic, pyroptotic and ferroptotic related genes related genes, while fatty acid oxidation were downregulated. Notably, treatment of HK-2 tubular human cells and THP-1 human monocytes with lupus nephritis serum provoked upregulated glycolysis and enhancement of pyroptosis and ferroptosis. Conclusions Collectively, our findings identify that pharmacological induction of lupus in vitro and in vivo provokes a metabolic switch toward glycolysis that provokes enhancement of ferroptosis and inflammatory/pyroptotic markers in both tubular epithelial cells and monocytes/macrophages since 2DG treatment reduces the ferroptosis and inflammatory marker upregulation. Indeed, this study provides a novel anti-LN treatment strategy targeting glycolysis activation in renal macrophages and renal tubular epithelial cells that prevents pyroptosis and ferroptosis cell death to reduced sustained LN tissue inflammation.
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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 | 0.000 | 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 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".