Homocysteine stimulates monocyte chemoattractant protein-1 expression in the kidney via nuclear factor-κB activation
Bibliographic record
Abstract
Hyperhomocysteinemia, or an elevation of blood homocysteine (Hcy) levels, is associated with cardiovascular disorders. Although kidney dysfunction is an important risk factor causing hyperhomocysteinemia, the direct effect of Hcy on the kidney is not well documented. There is a positive association between an elevation of blood Hcy levels and the development of chronic kidney disease. Inflammatory response such as increased chemokine expression has been implicated as one of the mechanisms for renal disease. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that is involved in the inflammatory response in renal disease. Nuclear factor-kappaB (NF-kappaB) plays an important role in upregulation of MCP-1 expression. We investigated the effect of hyperhomocysteinemia on MCP-1 expression and the molecular mechanism underlining such an effect in rat kidneys as well as in proximal tubular cells. Hyperhomocysteinemia was induced in rats fed a high-methionine diet for 12 wk. The MCP-1 mRNA expression and MCP-1 protein levels were significantly increased in kidneys isolated from hyperhomocysteinemic rats. The NF-kappaB activity was significantly increased in the same kidneys. Pretreatment of hyperhomocysteinemic rats with a NF-kappaB inhibitor abolished hyperhomocysteinemia-induced MCP-1 expression in the kidney. To confirm the causative role of NF-kappaB activation in MCP-1 expression, human kidney proximal tubular cells were transfected with decoy NF-kappaB oligodeoxynucleotide to inhibit NF-kappaB activation. Such a treatment prevented Hcy-induced MCP-1 mRNA expression in tubular cells. Our results suggest that hyperhomocysteinemia stimulates MCP-1 expression in the kidney via NF-kappaB activation. Such an inflammatory response may contribute to renal injury associated with hyperhomocysteinemia.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| 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".