Evidence map›Paper›PMID 22962618›Full record

ArticlePloS one2012

Secretion of soluble vascular endothelial growth factor receptor 1 (sVEGFR1/sFlt1) requires Arf1, Arf6, and Rab11 GTPases.

Jae-Joon Jung, Ajit Tiwari, Shivangi M Inamdar, Christie P Thomas, Apollina Goel, Amit Choudhury

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.3field-weighted citation impact, top 13% 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

21 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
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  6. ExploringPharmaceutics · 2023
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  20. The myosin motor Myo1c is required for VEGFR2 delivery to the cell surface and for angiogenic signaling.American journal of physiology. Heart and circulatory physiology · 2013
    Article
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Jae-Joon JungDepartments of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, United States of America.
Ajit Tiwari
Shivangi M Inamdar
Christie P Thomas
Apollina Goel
Amit Choudhury
University of Iowa · US

Funding

Role of Syntaxin 6 Regulated Post-Golgi Trafficking in AngiogenesisR01HL089599 · NHLBI · UNIVERSITY OF IOWA · PI CHOUDHURY, AMIT · 2008 to 2012
$1.9M
Expression of sFlt1 and its function in the glomerular endotheliumR01DK090053 · NIDDK · UNIVERSITY OF IOWA · PI THOMAS, CHRISTIE P. · 2010 to 2014
$1.6M
Chemoradiotherapy for Multiple MyelomaR01CA127958 · NCI · UNIVERSITY OF IOWA · PI GOEL, APOLLINA · 2009 to 2012
$1.1M
NCI NIH HHS R01CA127958NHLBI NIH HHS HL089599NHLBI NIH HHS R01 HL089599NIDDK NIH HHS R01 DK090053NIDDK NIH HHS R01DK090053
6 · The paper itself

Abstract

The soluble form of vascular endothelial growth factor receptor 1 (sVEGFR-1/sFlt1) is generated by alternative splicing of the FLT1 gene. Secretion of sFlt1 from endothelial cells plays an important role in blood vessel sprouting and morphogenesis. However, excess sFlt1 secretion is associated with diseases such as preeclampsia and chronic kidney disease. To date, the secretory transport process involved in the secretion of sFlt1 is poorly understood. In the present study, we investigated the itinerary of sFlt1 trafficking along the secretory pathway. To understand the timecourse of sFlt1 secretion, endothelial cells stably expressing sFlt1 were metabolically radiolabeled with [(35)S]-methionine and cysteine. Our results indicate that after initial synthesis the levels of secreted [(35)S]-sFlt1 in the extracellular medium peaks at 8 hours. Treatment with brefeldin A (BFA), a drug which blocks trafficking between the endoplasmic reticulum (ER) and the Golgi complex, inhibited extracellular release of sFlt1 suggesting that ER to Golgi and intra-Golgi trafficking of sFlt1 are essential for its secretion. Furthermore, we show that ectopic expression of dominant-negative mutant forms of Arf1, Arf6, and Rab11 as well as siRNA-mediated knockdown of these GTPases block secretion of sFlt1 during normoxic and hypoxic conditions suggesting role for these small GTPases. This work is the first to report role of regulatory proteins involved in sFlt1 trafficking along the secretory pathway and may provide insights and new molecular targets for the modulation of sFlt-1 release during physiological and pathological conditions.

Indexed as

ADP-Ribosylation Factor 1ADP-Ribosylation Factor 6ADP-Ribosylation FactorsAmino AcidsBrefeldin ACell Line, TumorEndoplasmic ReticulumGene ExpressionGolgi ApparatusHumansHuman Umbilical Vein Endothelial CellsPlasmidsProtein Structure, TertiaryProtein Synthesis InhibitorsProtein Transportrab11 GTP-Binding ProteinsADP-Ribosylation Factor 1ADP-Ribosylation Factor 6ADP-Ribosylation FactorsAmino AcidsARF6 protein, humanBrefeldin AProtein Synthesis Inhibitorsrab11 GTP-Binding Proteinsrab GTP-Binding ProteinsRNA, Small InterferingSulfur RadioisotopesVascular Endothelial Growth Factor Receptor-1

Identifiers

PMID22962618
PMCPMC3433446
OpenAlexW1987390440

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.