Evidence map›Paper›PMID 27643869›Full record

ArticleBone marrow transplantation2017

Thrombomodulin blocks calcineurin inhibitor-induced vascular permeability via inhibition of Src/VE-cadherin axis.

T Ikezoe, J Yang, C Nishioka, K Umezawa, A Yokoyama

Abstract read
PubMed Publisher
In one paragraph

Article in Bone marrow transplantation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

9 citing papers in PubMed, 17 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

5 authors at 2 institutions in 1 country.

T IkezoeDepartment of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Kochi, Japan.
J YangDepartment of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Kochi, Japan.
C NishiokaDepartment of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Kochi, Japan.
K UmezawaDepartment of Molecular Target Medicine Screening, School of Medicine, Aichi Medical University, Aichi, Japan.
A YokoyamaDepartment of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Kochi, Japan.
Kōchi University · JPAichi Medical University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recombinant human soluble thrombomodulin (rTM) counteracted capillary leakage and alleviated edema in individuals with sinusoidal obstruction syndrome and engraftment syndrome after hematopoietic stem cell transplantation. We previously showed that rTM increased levels of antiapoptotic protein Mcl-1 and protected endothelial cells from calcineurin inhibitor cyclosporine A (CsA)-induced apoptosis. However, the molecular mechanisms by which rTM enhances barrier function in vascular endothelial cells remain unknown. Here we show that exposure of vascular endothelial EA.hy926 cells to CsA induced phosphorylation of Src/vascular endothelial cadherin (VE-cadherin) and translocation of VE-cadherin from cell surface to cytoplasm, resulting in an increase in vascular permeability. In addition, CsA increased production of inflammatory cytokines, including interleukin (IL)-1β and IL-6, associated with an increase in nuclear levels of nuclear factor-κB (NF-κB) which also enhanced vascular permeability. Importantly, the fourth and fifth regions of epidermal growth factor-like domain of TM (TME45) attenuated CsA-induced p-Src/VE-cadherin and vascular permeability in parallel with a decrease in nuclear levels of NF-κB and cytokine production in EA.hy926 cells. In conclusion, TM, especially TME45, maintains vascular integrity, at least in part, via Src signaling.

Indexed as

AnimalsAntigens, CDCadherin 5CadherinsCalcineurin InhibitorsCapillary PermeabilityCell LineCyclosporineFemaleInterleukin-1betaInterleukin-6MiceMice, Inbred ICRMyeloid Cell Leukemia Sequence 1 Proteinsrc-Family KinasesThrombomodulinAntigens, CDCadherin 5CadherinsCalcineurin InhibitorsCyclosporineIL1B protein, mouseInterleukin-1betaInterleukin-6interleukin-6, mouseMcl1 protein, mouseMyeloid Cell Leukemia Sequence 1 Proteinsrc-Family KinasesTHBD protein, humanThrombomodulin

Identifiers

PMID27643869
OpenAlexW2521465596

What OpenQuestion holds

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Read underepoch 390

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.