New insights into the immune functions of podocytes: the role of complement
Bibliographic record
Abstract
Podocytes are differentiated epithelial cells which play an essential role to ensure a normal function of the glomerular filtration barrier (GFB). In addition to their adhesive properties in maintaining the integrity of the filtration barrier, they have other functions, such as synthesis of components of the glomerular basement membrane (GBM), production of vascular endothelial growth factor (VEGF), release of inflammatory proteins, and expression of complement components. They also participate in the glomerular crosstalk through multiple signalling pathways, including endothelin-1, VEGF, transforming growth factor β (TGFβ), bone morphogenetic protein 7 (BMP-7), latent transforming growth factor β-binding protein 1 (LTBP1), and extracellular vesicles.Growing literature suggests that podocytes share many properties of innate and adaptive immunity, supporting a multifunctional role ensuring a healthy glomerulus. As consequence, the "immune podocyte" dysfunction is thought to be involved in the pathogenesis of several glomerular diseases, referred to as "podocytopathies." Multiple factors like mechanical, oxidative, and/or immunologic stressors can induce cell injury. The complement system, as part of both innate and adaptive immunity, can also define podocyte damage by several mechanisms, such as reactive oxygen species (ROS) generation, cytokine production, and endoplasmic reticulum stress, ultimately affecting the integrity of the cytoskeleton, with subsequent podocyte detachment from the GBM and onset of proteinuria.Interestingly, podocytes are found to be both source and target of complement-mediated injury. Podocytes express complement proteins which contribute to local complement activation. At the same time, they rely on several protective mechanisms to escape this damage. Podocytes express complement factor H (CFH), one of the main regulators of the complement cascade, as well as membrane-bound complement regulators like CD46 or membrane cofactor protein (MCP), CD55 or decay-accelerating factor (DAF), and CD59 or defensin. Further mechanisms, like autophagy or actin-based endocytosis, are also involved to ensure podocyte homeostasis and protection against injury.This review will provide an overview of the immune functions of podocytes and their response to immune-mediated injury, focusing on the pathogenic link between complement and podocyte damage.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| 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".