Role of sCD89 Myeloid Receptor in Glomerular Hypercellularity in Childhood IgAN
Bibliographic record
Abstract
Background: Childhood immunoglobulin A nephropathy (cIgAN) is one of the most common primary glomerulonephritis. It manifests as recurrent hematuria and proteinuria, associated with renal inflammation and glomerular mesangial hypercellularity. Without early diagnosis and targeted treatment, up to 40% of patients may progress to end-stage renal disease within 20 years. This autoimmune disease is characterized by glomerular deposition of circulating immune complexes (CICs). Soluble CD89 (sCD89), present in CICs, plays a key role in inflammation and mesangial proliferation in cIgAN through the involvement of the transferrin receptor 1 (TfR1) and activation of the PI3K/mTOR pathway. However, the underlying molecular mechanisms remain poorly understood. In this study, we investigate the mechanisms by which sCD89 regulates TfR1, and the requirement of TfR1 in mediating sCD89-induced activation of the PI3K/Akt/mTOR signaling pathway in human mesangial cells (HMCs). Methods: HMCs were stimulated with recombinant sCD89 (rsCD89) and the expression of TfR1 was analyzed by RT-qPCR, western blot, immunofluorescence, and flow cytometry. In parallel, cells were treated with siRNA targeting TfR1, and the protein expression and phosphorylation of key components of the PI3K/Akt/mTOR pathway, including p70S6K1, 4E-BP1, and S6Rp, were analyzed by western blot. Results: TfR1 was found to be consistently expressed in HMCs and was upregulated at both mRNA and protein levels 24 hours after rsCD89 stimulation. HMC stimulation with rsCD89 also increased the expression and phosphorylation of Akt (p-T308, p-S473), mTOR (p-S2448), and p70S6K1 (p-T389), while their levels were markedly decreased when TfR1 was silenced. Conclusion: These findings strongly support the involvement of sCD89 in mesangial cell proliferation through its regulation on TfR1 expression and mTOR pathway activation. This study significantly advances our understanding of the the functional connections between sCD89, TfR1, and mTOR signaling, offering a promising foundation for new therapeutic approaches targeting mesangial hypercellularity and inflammation in cIgAN.
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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".