Endothelial AGGF1 contributes to glomerular barrier dysfunction via TNFSF12/FN14-Src-VE-cadherin signaling in diabetic kidney disease
- Design
- Animal study · Biomarker outcome
- Match to healthy normal-weight adults aged 55–75
- Not human evidenceVERY_INDIRECT: semaglutide was studied only in diabetic db/db mice and cultured cells.
- Could weight loss explain it?
- PossiblyNo body-weight, glucose or mediation data are reported for the semaglutide-treated mice, so weight and metabolic change are not separated from the kidney findings.
- Study tier
- Study tier 4VERY_LOW: a preclinical mouse and cell study in which the semaglutide result is a secondary finding.
- Assessment
- Version 2 · Two independent AI reviews agreed · Oct 19, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
This lab study looked at a protein called AGGF1 in kidney damage from diabetes, using patient kidney samples, diabetic mice and cells. In diabetic mice, semaglutide was associated with lower AGGF1 levels and better function of the kidney's filtering barrier, and raising AGGF1 in cells weakened semaglutide's effect. No numbers are given for the semaglutide results, and this is animal and cell evidence, not evidence in people.
01Findings
What the study reported
- Drugs
- Semaglutide
- Comparator
- not reported in abstract
- Primary outcome
- role of AGGF1 in glomerular endothelial barrier dysfunction in diabetic kidney disease
- Effect
- Semaglutide was associated with reduced renal AGGF1 expression and improved endothelial barrier-related outcomes in db/db mice; AGGF1 overexpression blunted semaglutide's effect on junctional proteins in high-glucose cells. No numbers reported.
- 95% confidence interval
- Not extracted
- Follow-up
- Not stated
- Adverse events
- not reported in abstract
- Limitations
- Mechanistic mouse and cell study; the semaglutide finding is secondary, unquantified in the abstract, and has no stated dose or group size.
Who was studied
- Obesity status
- not reported in abstract
- Diabetes status
- diabetes required (db/db mice; kidney samples from patients with diabetic kidney disease; type not stated)
- Cvd status
- not reported in abstract
- Ckd status
- diabetic kidney disease required (db/db mice; patient kidney samples)
- Baseline condition
- diabetic kidney disease (patient kidney samples; db/db mice)
Study quality details
- Study design
- Preclinical (animal)
- Sample size
- not extracted
- Randomization
- n/a
- Blinding
- not stated
- Comparator
- not reported in abstract
- Follow up duration
- not stated
- Outcome type
- biomarker
- Replication
- not assessed
- Consistency with other evidence
- not assessed
- Population applicability
- VERY_INDIRECT
- Statistical precision
- no CI reported
- Risk of bias
- not assessed
- Funding conflicts
- unclear
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- not stated in source
- Sponsor role
- not reported in abstract
- Author conflicts
- The authors declare no known competing financial interests or personal relationships.
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
Disruption of the glomerular filtration barrier (GFB) is a key feature of diabetic kidney disease (DKD), but the underlying mechanisms remain incompletely understood. We investigated the role of angiogenic factor 1 (AGGF1) in glomerular endothelial barrier dysfunction in DKD. AGGF1 expression was examined in kidney samples from patients with DKD and in db/db mice. We also used endothelial cell-specific Aggf1 knockout mice and in vitro endothelial cell experiments to assess the effects of AGGF1 on vascular leakage and endothelial junctions. AGGF1 expression was increased in kidneys from patients with DKD and db/db mice. Endothelial Aggf1 deletion reduced vascular leakage in diabetic mice. Mechanistically, AGGF1 promoted Src-dependent VE-cadherin phosphorylation and dissociation of the VE-cadherin/β-catenin complex. Semaglutide treatment was associated with reduced renal AGGF1 expression and improved endothelial barrier-related outcomes in db/db mice. In vitro, AGGF1 overexpression attenuated the beneficial effect of semaglutide on endothelial junctional proteins under high-glucose conditions. Together, these findings identify endothelial AGGF1 as a contributor to GFB dysfunction in DKD and suggest that it may be a potential therapeutic target.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Oct 18, 2026 | 42869327 first ingestion |