Evidence map›Paper›PMID 34440885›Full record

ArticleCells2021

A Novel Treatment for Glomerular Disease: Targeting the Activated Macrophage Folate Receptor with a Trojan Horse Therapy in Rats.

Gabriela E Garcia, Yingjuan J Lu, Luan D Truong, Carlos A Roncal-Jiménez, Makoto Miyazaki, Shinobu Miyazaki-Anzai, Gabriel Cara-Fuentes, Ana Andres-Hernando, Miguel Lanaspa, Richard J Johnson and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.6field-weighted citation impact, top 29% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Monocytes and Macrophages in Kidney Disease and Homeostasis.International journal of molecular sciences · 2024
    Review
  2. Article
  3. Article
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

11 authors at 4 institutions in 1 country.

Gabriela E GarciaDepartment of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Yingjuan J LuEndocyte, Inc., Novartis Institutes for Biomedical Research, West Lafayette, IN 47906, USA.
Luan D TruongDepartment of Pathology, The Houston Methodist Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
Carlos A Roncal-JiménezDepartment of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Makoto MiyazakiDepartment of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Shinobu Miyazaki-AnzaiDepartment of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Gabriel Cara-FuentesDepartment of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Ana Andres-HernandoDepartment of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Miguel LanaspaDepartment of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Richard J JohnsonDepartment of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Christopher P LeamonEndocyte, Inc., Novartis Institutes for Biomedical Research, West Lafayette, IN 47906, USA.
University of Colorado Anschutz Medical Campus · USBaylor College of Medicine · USEndocyte (United States) · USNovartis (United States) · US

Funding

The role of MLKL in the regulation of vascular calcification in CKDR01HL132318 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI MIYAZAKI, MAKOTO · 2016 to 2025
$3.8M
A Novel Driver of Hyperphosphatemia and Vascular Calcification in CKDR01DK124901 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI BLAINE, JUDITH T.,, MIYAZAKI, MAKOTO · 2021 to 2024
$1.9M
The contributory role of microbial metabolite in the pathogenesis of CKD-dependent vascular calcificationR01HL133545 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI MIYAZAKI, MAKOTO · 2018 to 2021
$1.9M
NHLBI NIH HHS R01 HL132318NHLBI NIH HHS R01 HL133545NIDDK NIH HHS R01 DK124901NIH HHS DK082509
6 · The paper itself

Abstract

Since activated macrophages express a functional folate receptor β (FRβ), targeting this macrophage population with folate-linked drugs could increase selectivity to treat inflammatory diseases. Using a macrophage-mediated anti-glomerular basement membrane (anti-GBM) glomerulonephritis (GN) in WKY rats, we investigated the effect of a novel folic acid-aminopterin (AMT) conjugate (EC2319) designed to intracellularly deliver AMT via the FR. We found that treatment with EC2319 significantly attenuated kidney injury and preserved renal function. Kidney protection with EC2319 was blocked by a folate competitor, indicating that its mechanism of action was specifically FRβ-mediated. Notably, treatment with methotrexate (MTX), another folic acid antagonist related to AMT, did not protect from kidney damage. EC2319 reduced glomerular and interstitial macrophage infiltration and decreased M1 macrophage recruitment but not M2 macrophages. The expression of CCL2 and the pro-fibrotic cytokine TGF-β were also reduced in nephritic glomeruli with EC2319 treatment. In EC2319-treated rats, there was a significant decrease in the deposition of collagens. In nephritic kidneys, FRβ was expressed on periglomerular macrophages and macrophages present in the crescents, but its expression was not observed in normal kidneys. These data indicate that selectively targeting the activated macrophage population could represent a novel means for treating anti-GBM GN and other acute crescentic glomerulonephritis.

Indexed as

AminopterinAnimalsFibrosisFolate Receptor 2Folic AcidGlomerulonephritisInflammationMacrophagesMethotrexateRatsAminopterinFolate Receptor 2Folic AcidMethotrexateaminopterinfibrosisfolate receptorglomerulonephritisinflammationmacrophages

Identifiers

PMID34440885
PMCPMC8393837
OpenAlexW3193527648

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.