Evidence map›Paper›PMID 38637347›Full record

ArticleEJNMMI radiopharmacy and chemistry2024

Radiolabeled 15-mer peptide internalization is mediated by megalin (LRP2 receptor) in a CRISPR/Cas9-based LRP2 knockout human kidney cell model.

Anna Durinova, Lucie Smutna, Pavel Barta, Rajamanikkam Kamaraj, Tomas Smutny, Bernhard Schmierer, Petr Pavek, Frantisek Trejtnar

Open access · goldAbstract read
In one paragraph

Article in EJNMMI radiopharmacy and chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

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

8 authors at 2 institutions in 2 countries.

Anna DurinovaDivision of Radiopharmacy, Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic.
Lucie SmutnaDivision of Radiopharmacy, Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic. hyrsl7aa@faf.cuni.cz.ORCID http://orcid.org/0000-0002-3941-4193
Pavel BartaDepartment of Biophysics and Physical Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic.
Rajamanikkam KamarajDivision of Radiopharmacy, Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic.
Tomas SmutnyDivision of Radiopharmacy, Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic.
Bernhard SchmiererSciLifeLab and Department of Medical Biochemistry and Biophysics, CRISPR Functional Genomics, Karolinska Institutet, Solna, Sweden.
Petr PavekDivision of Radiopharmacy, Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic.
Frantisek TrejtnarDivision of Radiopharmacy, Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic.
Charles University · CZScience for Life Laboratory · SE

Funding

Grantová Agentura, Univerzita Karlova 150120NETPHARM CZ.02.01.01/00/22_008/0004607
6 · The paper itself

Abstract

backgroundMegalin (LRP2 receptor) mediates the endocytosis of radiolabeled peptides into proximal tubular kidney cells, which may cause nephrotoxicity due to the accumulation of a radioactive tracer. The study aimed to develop a cellular model of human kidney HK2 cells with LRP2 knockout (KO) using CRISPR/Cas9 technique. This model was employed for the determination of the megalin-mediated accumulation of

resultsThe gene editing in the LRP2 KO model was verified by testing two well-known megalin ligands when higher viability of KO cells was observed after gentamicin treatment at cytotoxic concentrations and lower FITC-albumin internalization by the KO cells was detected in accumulation studies. Fluorescent-activated cell sorting was used to separate genetically modified LRP2 KO cell subpopulations. Moreover, flow cytometry with a specific antibody against megalin confirmed LRP2 knockout. The verified KO model identified both

conclusionThe CRISPR/Cas9 knockout of LRP2 in human kidney HK2 cells is an effective approach for the determination of radiopeptide internalization mediated by megalin. This in vitro method provided direct molecular evidence for the cellular uptake of radiolabeled anti-VEGFR 15-mer peptides via megalin.

Indexed as

CRISPR/Cas9LRP2MegalinRadiolabeled peptideRadionephrotoxicity

Identifiers

PMID38637347
PMCPMC11026318
OpenAlexW4394912003

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Registered trials

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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.