Evidence map›Paper›PMID 25858967›Full record

ArticleJournal of the American Society of Nephrology : JASN2015

A Podocyte-Based Automated Screening Assay Identifies Protective Small Molecules.

Ha Won Lee, Samia Q Khan, Mohd Hafeez Faridi, Changli Wei, Nicholas J Tardi, Mehmet M Altintas, Hatem A Elshabrawy, Steve Mangos, Kevin L Quick, Sanja Sever and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of the American Society of Nephrology : JASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
6.8field-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

42 citing papers in PubMed, 64 citations in OpenAlex.

  1. Article
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  4. Article
  5. Article
  6. A Small Molecule Agonist of Krüppel-Like Factor 15 in Proteinuric Kidney Disease.Journal of the American Society of Nephrology : JASN · 2024
    Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. The ShGlomFrontiers in cell and developmental biology · 2022
    Article
  14. Role of actin cytoskeleton in podocytes.Pediatric nephrology (Berlin, Germany) · 2021
    Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

12 authors at 2 institutions in 1 country.

Ha Won LeeDepartment of Medicine, Rush University Medical Center, Chicago, Illinois;
Samia Q KhanDepartment of Medicine, Rush University Medical Center, Chicago, Illinois;
Mohd Hafeez FaridiDepartment of Medicine, Rush University Medical Center, Chicago, Illinois;
Changli WeiDepartment of Medicine, Rush University Medical Center, Chicago, Illinois;
Nicholas J TardiDepartment of Medicine, Rush University Medical Center, Chicago, Illinois;
Mehmet M AltintasDepartment of Medicine, Rush University Medical Center, Chicago, Illinois;
Hatem A ElshabrawyDepartment of Medicine, Rush University Medical Center, Chicago, Illinois;
Steve MangosDepartment of Medicine, Rush University Medical Center, Chicago, Illinois;
Kevin L QuickCellular Imaging and Analysis, PerkinElmer Life Sciences, Waltham, Massachusetts; and.
Sanja SeverDepartment of Medicine, Harvard Medical School, Division of Nephrology, Massachusetts General Hospital, Charlestown, Massachusetts.
Jochen ReiserDepartment of Medicine, Rush University Medical Center, Chicago, Illinois; jochen_reiser@rush.edu vineet_gupta@rush.edu.
Vineet GuptaDepartment of Medicine, Rush University Medical Center, Chicago, Illinois; jochen_reiser@rush.edu vineet_gupta@rush.edu.
Rush University Medical Center · USMassachusetts General Hospital · US

Funding

Translating oral CD11b agonist as a novel therapeutic for lupus nephritisR01DK084195 · NIDDK · UNIVERSITY OF TEXAS MED BR GALVESTON · PI VINEET GUPTA, Timothy B Niewold · 2011 to 2026
$5.7M
Use of small molecules that stabilize dynamin rings in podocytopathiesR01DK087985 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI SEVER, SANJA · 2011 to 2020
$3.4M
Role of Circulating suPAR in FSGSR01DK101350 · NIDDK · RUSH UNIVERSITY MEDICAL CENTER · PI REISER, JOCHEN · 2013 to 2017
$2.6M
Proteolytic Regulation of Podocyte Function by Cathepsin L.R01DK073495 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI REISER, JOCHEN · 2006 to 2015
$2.4M
Leukadherins as novel compounds for treating restenosisR01HL109582 · NHLBI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI GUPTA, VINEET, VAZQUEZ PADRON, ROBERTO IRENARDO · 2012 to 2015
$1.7M
Glomerular Disease Mechanisms mediated by Podocyte TRPC6R01DK089394 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI REISER, JOCHEN · 2010 to 2014
$1.6M
NHLBI NIH HHS HL109582NHLBI NIH HHS R01 HL109582NIDDK NIH HHS DK073495NIDDK NIH HHS DK084195NIDDK NIH HHS DK089394NIDDK NIH HHS DK101350NIDDK NIH HHS R01 DK073495NIDDK NIH HHS R01 DK084195NIDDK NIH HHS R01 DK087985NIDDK NIH HHS R01 DK089394NIDDK NIH HHS R01 DK101350
6 · The paper itself

Abstract

Podocyte injury and loss mark an early step in the pathogenesis of various glomerular diseases, making these cells excellent targets for therapeutics. However, cell-based high-throughput screening assays for the rational development of podocyte-directed therapeutics are currently lacking. Here, we describe a novel high-content screening-based phenotypic assay that analyzes thousands of podocytes per assay condition in 96-well plates to quantitatively measure dose-dependent changes in multiple cellular features. Our assay consistently produced a Z' value >0.44, making it suitable for compound screening. On screening with >2100 pharmacologically active agents, we identified 24 small molecules that protected podocytes against injury in vitro (1% hit rate). Among the identified hits, we confirmed an β1-integrin agonist, pyrintegrin, as a podocyte-protective agent. Treatment with pyrintegrin prevented damage-induced decreases in F-actin stress fibers, focal adhesions, and active β1-integrin levels in cultured cells. In vivo, administration of pyrintegrin protected mice from LPS-induced podocyte foot process effacement and proteinuria. Analysis of the murine glomeruli showed that LPS administration reduced the levels of active β1 integrin in the podocytes, which was prevented by cotreatment with pyrintegrin. In rats, pyrintegrin reduced peak proteinuria caused by puromycin aminonucleoside-induced nephropathy. Our findings identify pyrintegrin as a potential therapeutic candidate and show the use of podocyte-based screening assays for identifying novel therapeutics for proteinuric kidney diseases.

Indexed as

ActinsAlbuminuriaAnimalsCell MovementEpithelial CellsFocal AdhesionsHigh-Throughput Screening AssaysHydroxyquinolinesIntegrin beta1Kidney DiseasesKidney GlomerulusLipopolysaccharidesMiceMicroscopy, ConfocalPhenotypePodocytesActinsHydroxyquinolinesIntegrin beta1LipopolysaccharidesPuromycin AminonucleosidepyrintegrinSulfonamidesadhesion moleculeglomerular diseaseglomerular epithelial cells

Identifiers

PMID25858967
PMCPMC4625676
OpenAlexW2144807905

What OpenQuestion holds

Textmetadata
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.