Evidence mapPaperPMID 38474393Full record

ArticleCells2024

Advanced Glycation End Products Upregulate CD40 in Human Retinal Endothelial and Müller Cells: Relevance to Diabetic Retinopathy.

Jose-Andres C Portillo, Amelia Pfaff, Sarah Vos, Matthew Weng, Ram H Nagaraj, Carlos S Subauste

Open access · goldAbstract read
In one paragraph

Article in Cells, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
6.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
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  4. Article
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  6. Article
  7. Diabetic retinopathy and Alzheimer's disease: Convergence of the unfolded protein response in neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
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  9. Article
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  12. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Jose-Andres C PortilloDivision of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Amelia PfaffDivision of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Sarah VosDivision of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Matthew WengDivision of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Ram H NagarajDepartment of Ophthalmology, University of Colorado, Aurora, CO 80045, USA.ORCID 0000-0003-4737-8847
Carlos S SubausteDivision of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Case Western Reserve University · USUniversity of Colorado Anschutz Medical Campus · US

Funding

The Specialized Animal Resources CoreP30EY011373 · CASE WESTERN RESERVE UNIVERSITY · 1997 to 2025
$3.9M
NEI NIH HHS EY019250NEI NIH HHS P30 EY011373NEI NIH HHS P30 EY11373NEI NIH HHS R01 EY019250
6 · The paper itself

Abstract

CD40 induces pro-inflammatory responses in endothelial and Müller cells and is required for the development of diabetic retinopathy (DR). CD40 is upregulated in these cells in patients with DR. CD40 upregulation is a central feature of CD40-driven inflammatory disorders. What drives CD40 upregulation in the diabetic retina remains unknown. We examined the role of advanced glycation end products (AGEs) in CD40 upregulation in endothelial cells and Müller cells. Human endothelial cells and Müller cells were incubated with unmodified or methylglyoxal (MGO)-modified fibronectin. CD40 expression was assessed by flow cytometry. The expression of ICAM-1 and CCL2 was examined by flow cytometry or ELISA after stimulation with CD154 (CD40 ligand). The expression of carboxymethyl lysine (CML), fibronectin, and laminin as well as CD40 in endothelial and Müller cells from patients with DR was examined by confocal microscopy. Fibronectin modified by MGO upregulated CD40 in endothelial and Müller cells. CD40 upregulation was functionally relevant. MGO-modified fibronectin enhanced CD154-driven upregulation of ICAM-1 and CCL2 in endothelial and Müller cells. Increased CD40 expression in endothelial and Müller cells from patients with DR was associated with increased CML expression in fibronectin and laminin. These findings identify AGEs as inducers of CD40 upregulation in endothelial and Müller cells and enhancers of CD40-dependent pro-inflammatory responses. CD40 upregulation in these cells is associated with higher CML expression in fibronectin and laminin in patients with DR. This study revealed that CD40 and AGEs, two important drivers of DR, are interconnected.

Indexed as

Diabetes MellitusDiabetic RetinopathyCD40 AntigensCD40 LigandEndothelial CellsEpendymoglial CellsFibronectinsGlycation End Products, AdvancedHumansIntercellular Adhesion Molecule-1LamininMagnesium OxideRetinaCD40 AntigensCD40 LigandFibronectinsGlycation End Products, AdvancedIntercellular Adhesion Molecule-1LamininMagnesium Oxideadhesion moleculechemokinediabetesfibronectininflammationlamininretina

Identifiers

PMID38474393
PMCPMC10930611
OpenAlexW4392286605

What Socratic holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.