| Title |
VEGF isoforms have differential effects on permeability of human pulmonary microvascular endothelial cells
|
|---|---|
| Published in |
Respiratory Research, June 2017
|
| DOI | 10.1186/s12931-017-0602-1 |
| Pubmed ID | |
| Authors |
Khadija Ourradi, Thomas Blythe, Caroline Jarrett, Shaney L. Barratt, Gavin I. Welsh, Ann B. Millar |
| Abstract |
Alternative splicing of Vascular endothelial growth factor-A mRNA transcripts (commonly referred as VEGF) leads to the generation of functionally differing isoforms, the relative amounts of which have potentially significant physiological outcomes in conditions such as acute respiratory distress syndrome (ARDS). The effect of such isoforms on pulmonary vascular permeability is unknown. We hypothesised that VEGF165a and VEGF165b isoforms would have differing effects on pulmonary vascular permeability caused by differential activation of intercellular signal transduction pathways. To test this hypothesis we investigated the physiological effect of VEGF165a and VEGF165b on Human Pulmonary Microvascular Endothelial Cell (HPMEC) permeability using three different methods: trans-endothelial electrical resistance (TEER), Electric cell-substrate impedance sensing (ECIS) and FITC-BSA passage. In addition, potential downstream signalling pathways of the VEGF isoforms were investigated by Western blotting and the use of specific signalling inhibitors. VEGF165a increased HPMEC permeability using all three methods (paracellular and transcellular) and led to associated VE-cadherin and actin stress fibre changes. In contrast, VEGF165b decreased paracellular permeability and did not induce changes in VE-cadherin cell distribution. Furthermore, VEGF165a and VEGF165b had differing effects on both the phosphorylation of VEGF receptors and downstream signalling proteins pMEK, p42/44MAPK, p38 MAPK, pAKT and peNOS. Interestingly specific inhibition of the pMEK, p38 MAPK, PI3 kinase and eNOS pathways blocked the effects of both VEGF165a and VEGF165b on paracellular permeability and the effect of VEGF165a on proliferation/migration, suggesting that this difference in cellular response is mediated by an as yet unidentified signalling pathway(s). This study demonstrates that the novel isoform VEGF165a and VEGF165b induce differing effects on permeability in pulmonary microvascular endothelial cells. |
X Demographics
The data shown below were collected from the profiles of 8 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 3 | 38% |
| United States | 2 | 25% |
| Unknown | 3 | 38% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 6 | 75% |
| Science communicators (journalists, bloggers, editors) | 1 | 13% |
| Scientists | 1 | 13% |
Mendeley readers
The data shown below were compiled from readership statistics for 51 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 2% |
| Unknown | 50 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 13 | 25% |
| Researcher | 6 | 12% |
| Student > Bachelor | 5 | 10% |
| Student > Master | 5 | 10% |
| Student > Postgraduate | 4 | 8% |
| Other | 6 | 12% |
| Unknown | 12 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 11 | 22% |
| Biochemistry, Genetics and Molecular Biology | 10 | 20% |
| Agricultural and Biological Sciences | 7 | 14% |
| Neuroscience | 2 | 4% |
| Psychology | 2 | 4% |
| Other | 8 | 16% |
| Unknown | 11 | 22% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 June 2018.
All research outputs
#7,899,670
of 25,382,440 outputs
Outputs from Respiratory Research
#1,038
of 3,062 outputs
Outputs of similar age
#117,593
of 331,648 outputs
Outputs of similar age from Respiratory Research
#41
of 79 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 3,062 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.9. This one has gotten more attention than average, scoring higher than 65% of its peers.
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We're also able to compare this research output to 79 others from the same source and published within six weeks on either side of this one. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.