Sensing Iron: Reciprocal Regulation of Hepcidin mRNA by Soluble and Cell-Associated Hemojuvelin.
Bibliographic record
Abstract
Abstract Human genetic studies identified HJV (also called HFE2) as the major cause for juvenile hemochromatosis (JH). Patients with HJV hemochromatosis have low urinary levels of hepcidin, the principal iron-regulatory hormone secreted by the liver. We attempted to establish the specific roles of HJV in iron metabolism, especially its relationship with hepcidin. Translation of the genomic sequence indicated a C-terminal GPI anchor for the protein product of HJV, hemojuvelin. This suggested that hemojuvelin may have either a soluble or a cell-associated form. In human hepatoma cell line Hep3B, knockdown of cellular HJV by siRNA decreased hepcidin expression, independently of the IL-6 pathway. Intriguingly, the addition of recombinant soluble hemojuvelin (rs-hemojuvelin) also suppressed hepcidin expression in primary human hepatocytes, in a log-linear dose-dependent manner, suggesting competition between soluble and cell-associated forms of hemojuvelin. Soluble hemojuvelin was found in human sera at concentrations similar to those required to suppress hepcidin mRNA in vitro. In cells engineered to express hemojuvelin, soluble hemojuvelin release was progressively inhibited by increasing iron or holotransferrin concentrations. Our study suggests that soluble and cell-associated hemojuvelin reciprocally regulate hepcidin mRNA levels, and that hemojuvelin may serve as a molecular messenger for iron homeostasis. Even in hepatocytes stimulated with IL-6, we observed strong suppression of hepcidin mRNA by rs-hemojuvelin. If rs-hemojuvelin or its active fragments also suppress hepcidin production in vivo, they could be used to alleviate anemia of 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".