The role of VEGF-A in glomerular development and function
Bibliographic record
Abstract
PURPOSE OF REVIEW: Vascular endothelial growth factor is a major regulator of blood vessel biology and is highly expressed in presumptive and mature podocytes within the glomerulus. It has long been recognized that dysregulation of this factor occurs in a number of glomerular diseases; however, definitive proof that it plays a pathogenic or developmental role in glomerular biology has remained elusive. This review will summarize some of the recent advances in our understanding of the role(s) of VEGF in these processes. RECENT FINDINGS: Gene targeting in the mouse has shown that tight regulation of vascular endothelial growth factor is required for development and maintenance of the glomerular filtration barrier. Podocyte-specific deletion of both alleles leads to congenital nephropathy and perinatal lethality. The glomeruli of mice that lack the 164 and 184 isoforms but express the 120 isoform, are smaller and have fewer capillary loops, whereas mice with podocyte-specific haploinsufficiency for all isoforms develop glomerular endotheliosis, the renal lesion seen in preeclampsia. Elevated levels of the soluble vascular endothelial growth factor receptor 1, which binds and inhibits circulating forms of VEGF were identified in patients with preeclampsia; rats injected with this soluble receptor develop hypertension, endotheliosis and proteinuria, similar to the lesion seen in podocyte-specific haploinsufficient VEGF mice. Conversely, podocyte-specific overexpression of the 164 isoform leads to collapsing glomerulopathy, the classic lesion seen in HIV-associated nephropathy. SUMMARY: These results demonstrate that vascular endothelial growth factor plays a critical role in glomerular development and function, and provides the foundation to develop novel diagnostic or therapeutic tools for patients with glomerular disease.
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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 | 0.001 |
| 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 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".