Evidence map›Paper›PMID 39947471›Full record

ArticleThe Journal of biological chemistry2025

Integrin beta 1 and fibronectin mediate extracellular vesicle uptake and functional RNA delivery.

Omnia M Elsharkasy, Willemijn S de Voogt, Maria Laura Tognoli, Leanne van der Werff, Jerney J Gitz-Francois, Cornelis W Seinen, Raymond M Schiffelers, Olivier G de Jong, Pieter Vader

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
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

17 citing papers in PubMed.

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  14. Secretion of Extracellular Microvesicles Induced by a Fraction ofInternational journal of molecular sciences · 2025
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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

9 authors.

Omnia M ElsharkasyCDL Research, University Medical Center Utrecht, Utrecht, The Netherlands.
Willemijn S de VoogtCDL Research, University Medical Center Utrecht, Utrecht, The Netherlands.
Maria Laura TognoliCDL Research, University Medical Center Utrecht, Utrecht, The Netherlands.
Leanne van der WerffCDL Research, University Medical Center Utrecht, Utrecht, The Netherlands.
Jerney J Gitz-FrancoisCDL Research, University Medical Center Utrecht, Utrecht, The Netherlands.
Cornelis W SeinenCDL Research, University Medical Center Utrecht, Utrecht, The Netherlands.
Raymond M SchiffelersCDL Research, University Medical Center Utrecht, Utrecht, The Netherlands.
Olivier G de JongCDL Research, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands.
Pieter VaderCDL Research, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: pvader@umcutrecht.nl.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Extracellular vesicles (EVs) are cell-derived vesicles secreted by all cell types into the extracellular spaces. EVs comprise a heterogenous population of vesicles that carry bioactive molecules, such as proteins, lipids, and RNAs, which they can deliver to recipient cells. Over the past few years, EVs have been recognized for their vital role in intercellular communication, and thereby in various physiological and pathological processes. In addition, EVs are increasingly being studied as potential drug delivery vehicles. It is therefore crucial to understand the mechanisms and molecular players underlying EV uptake and functional cargo delivery. Several studies have investigated various EV uptake pathways; nonetheless, molecular mechanisms governing uptake and cargo transfer remain largely lacking. Here, we show, using a CRISPR/Cas9-mediated reporter system, that integrin β1 on recipient cells plays an important role in EV uptake and EV-mediated RNA delivery. Additionally, using both RNA interference and blocking antibodies, we show that association of integrin β1 with integrin α4 is essential for this process. We demonstrate that α4β1 on recipient cells interacts with EVs through surface localized fibronectin via binding to its leucine-aspartic acid-valine motif, and that blocking of this interaction reduces both EV uptake and RNA delivery. Thus, we identify a key mechanism in EV uptake and cargo delivery which could potentially facilitate research into EV biology and pave the way for the development of novel therapeutic approaches by targeting pathways that lead to functional cargo delivery.

Indexed as

Extracellular VesiclesFibronectinsIntegrin beta1RNAAnimalsCRISPR-Cas SystemsHumansFibronectinsIntegrin beta1Itgb1 protein, humanRNAEV uptakeextracellular vesiclesfibronectinintegrinsRNA delivery

Identifiers

PMID39947471
PMCPMC12020920

What OpenQuestion holds

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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.