Evidence map›Paper›PMID 34041925›Full record

ArticleJournal of the American Heart Association2021

MFG-E8 Regulates Vascular Smooth Muscle Cell Migration Through Dose-Dependent Mediation of Actin Polymerization.

Hou-Yu Chiang, Pao-Hsien Chu, Shao-Chi Chen, Ting-Hein Lee

Open access · goldAbstract read
In one paragraph

Article in Journal of the American Heart Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.4field-weighted citation impact, top 43% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

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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

4 authors at 1 institution in 1 country.

Hou-Yu ChiangDepartment of Anatomy College of Medicine Chang Gung University Taoyuan Taiwan.
Pao-Hsien ChuDivision of Cardiology Department of Internal Medicine Chang Gung Memorial Hospital Linkou Taiwan.
Shao-Chi ChenDepartment of Anatomy College of Medicine Chang Gung University Taoyuan Taiwan.
Ting-Hein LeeDepartment of Anatomy College of Medicine Chang Gung University Taoyuan Taiwan.
Chang Gung University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background Migration of vascular smooth muscle cells (VSMCs) is the main contributor to neointimal formation. The Arp2/3 (actin-related proteins 2 and 3) complex activates actin polymerization and is involved in lamellipodia formation during VSMC migration. Milk fat globule-epidermal growth factor 8 (MFG-E8) is a glycoprotein expressed in VSMCs. We hypothesized that MFG-E8 regulates VSMC migration through modulation of Arp2/3-mediated actin polymerization. Methods and Results To determine whether MFG-E8 is essential for VSMC migration, a model of neointimal hyperplasia was induced in the common carotid artery of wild-type and MFG-E8 knockout mice, and the extent of neointimal formation was evaluated. Genetic deletion of MFG-E8 in mice attenuated injury-induced neointimal hyperplasia. Cultured VSMCs deficient in MFG-E8 exhibited decreased cell migration. Immunofluorescence and immunoblotting revealed decreased Arp2 but not Arp3 expression in the common carotid arteries and VSMCs deficient in MFG-E8. Exogenous administration of recombinant MFG-E8 biphasically and dose-dependently regulated the cultured VSMCs. At a low concentration, MFG-E8 upregulated Arp2 expression. By contrast, MFG-E8 at a high concentration reduced the Arp2 level and significantly attenuated actin assembly. Arp2 upregulation mediated by low-dose MFG-E8 was abolished by treating cultured VSMCs with β1 integrin function-blocking antibody and Rac1 inhibitors. Moreover, treatment of the artery with a high dose of recombinant MFG-E8 diminished injury-induced neointimal hyperplasia and reduced VSMC migration. Conclusions MFG-E8 plays a critical role in VSMC migration through dose-dependent regulation of Arp2-mediated actin polymerization. These findings suggest that high doses of MFG-E8 may have therapeutic potential for treating vascular occlusive diseases.

Indexed as

Gene Expression RegulationActinsAnimalsAntigens, SurfaceApoptosisArterial Occlusive DiseasesCarotid Artery, CommonCell MovementCell ProliferationCells, CulturedDisease Models, AnimalDNAFemaleMaleMiceMice, KnockoutActinsAntigens, SurfaceDNAMfge8 protein, mouseMilk ProteinsArp2/3 complexMFG‐E8migrationneointimal formationvascular smooth muscle cells

Identifiers

PMID34041925
PMCPMC8483510
OpenAlexW3165295873

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.