Evidence map›Paper›PMID 26674641›Full record

ArticleStem cell research & therapy2015

Synergism of MSC-secreted HGF and VEGF in stabilising endothelial barrier function upon lipopolysaccharide stimulation via the Rac1 pathway.

Yi Yang, Qi-Hong Chen, Ai-Ran Liu, Xiu-Ping Xu, Ji-Bin Han, Hai-Bo Qiu

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

62 citing papers in PubMed, 97 citations in OpenAlex.

  1. Review
  2. The PPARβ/Delta-Induced Mesenchymal Stromal Cell Secretome Has Cytoprotective Effects via ANGPTL4 in a Pre-Clinical Model of Acute Lung Inflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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  14. The ARDS microenvironment enhances MSC-induced repair via VEGF in experimental acute lung inflammation.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  15. Is the endotoxin-complement cascade the major driver in lipedema?Trends in endocrinology and metabolism: TEM · 2024
    Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. Review

2 more citing papers are in PubMed but not listed here.

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

6 authors at 1 institution in 1 country.

Yi YangDepartment of Critical Care Medicine, Zhong-Da Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, People's Republic of China. yiyiyang2004@163.com.
Qi-Hong ChenDepartment of Critical Care Medicine, Zhong-Da Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, People's Republic of China. chenqihong00@163.com.
Ai-Ran LiuDepartment of Critical Care Medicine, Zhong-Da Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, People's Republic of China. airanliu2013@gmail.com.
Xiu-Ping XuDepartment of Critical Care Medicine, Zhong-Da Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, People's Republic of China. xiupxu@126.com.
Ji-Bin HanDepartment of Critical Care Medicine, Zhong-Da Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, People's Republic of China. hanjibin86@foxmail.com.
Hai-Bo QiuDepartment of Critical Care Medicine, Zhong-Da Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, People's Republic of China. haiboq2000@163.com.
Zhongda Hospital Southeast University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMesenchymal stem cells (MSCs) stabilise endothelial barrier function in acute lung injury via paracrine hepatocyte growth factor (HGF). Vascular endothelial growth factor (VEGF), which is secreted by MSCs, is another key regulator of endothelial permeability; however, its role in adjusting permeability remains controversial. In addition, whether an interaction occurs between HGF and VEGF, which are secreted by MSCs, is not completely understood.

methodsWe introduced a co-cultured model of human pulmonary microvascular endothelial cells (HPMECs) and MSC conditioned medium (CM) collected from MSCs after 24 h of hypoxic culture. The presence of VEGF and HGF in the MSC-CM was neutralised by anti-VEGF and anti-HGF antibodies, respectively. To determine the roles and mechanisms of MSC-secreted HGF and VEGF, we employed recombinant humanised HGF and recombinant humanised VEGF to co-culture with HPMECs. Additionally, we employed the RhoA inhibitor C3 transferase and the Rac1 inhibitor NSC23766 to inhibit the activities of RhoA and Rac1 in HPMECs treated with MSC-CM or VEGF/HGF with the same dosage as in the MSC-CM. Then, endothelial paracellular and transcellular permeability was detected. VE-cadherin, occludin and caveolin-1 protein expression in HPMECs was measured by western blot. Adherens junction proteins, including F-actin and VE-cadherin, were detected by immunofluorescence.

resultsMSC-CM treatment significantly decreased lipopolysaccharide-induced endothelial paracellular and transcellular permeability, which was significantly inhibited by pretreatment with HGF antibody or with both VEGF and HGF antibodies. Furthermore, MSC-CM treatment increased the expression of the endothelial intercellular adherence junction proteins VE-cadherin and occludin and decreased the expression of caveolin-1 protein. MSC-CM treatment also decreased endothelial apoptosis and induced endothelial cell proliferation; however, the effects of MSC-CM treatment were inhibited by pretreatment with HGF antibody or with both HGF and VEGF antibodies. Additionally, the effects of MSC-CM and VEGF/HGF on reducing endothelial paracellular and transcellular permeability were weakened when HPMECs were pretreated with the Rac1 inhibitor NSC23766.

conclusionHGF secreted by MSCs protects the endothelial barrier function; however, VEGF secreted by MSCs may synergize with HGF to stabilise endothelial cell barrier function. Rac1 is the pathway by which MSC-secreted VEGF and HGF regulate endothelial permeability.

Indexed as

ActinsAntigens, CDApoptosisCadherin 5CadherinsCapillary PermeabilityCaveolin 1Cell SurvivalCoculture TechniquesCulture Media, ConditionedEndothelial CellsHepatocyte Growth FactorHumansLipopolysaccharidesMesenchymal Stem Cellsrac1 GTP-Binding ProteinActinsAntigens, CDCadherin 5CadherinsCAV1 protein, humanCaveolin 1Culture Media, ConditionedHepatocyte Growth FactorHGF protein, humanLipopolysaccharidesrac1 GTP-Binding ProteinRAC1 protein, humanrhoA GTP-Binding ProteinRHOA protein, humanVascular Endothelial Growth Factor AVEGFA protein, human

Identifiers

PMID26674641
PMCPMC4682264
OpenAlexW2209240269

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LicenceCC BY
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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.