| Title |
Alk5/Runx1 signaling mediated by extracellular vesicles promotes vascular repair in acute respiratory distress syndrome
|
|---|---|
| Published in |
Clinical and Translational Medicine, June 2018
|
| DOI | 10.1186/s40169-018-0197-2 |
| Pubmed ID | |
| Authors |
Trushil Shah, Shanshan Qin, Mona Vashi, Dan N. Predescu, Niranjan Jeganathan, Cristina Bardita, Balaji Ganesh, Salvatore diBartolo, Louis F. Fogg, Robert A. Balk, Sanda A. Predescu |
| Abstract |
Pulmonary endothelial cells' (ECs) injury and apoptotic death are necessary and sufficient for the pathogenesis of the acute respiratory distress syndrome (ARDS), regardless of epithelial damage. Interaction of dysfunctional ECs with circulatory extracellular vesicles (EVs) holds therapeutic promise in ARDS. However, the presence in the blood of long-term ARDS survivors of EVs with a distinct phenotype compared to the EVs of non-surviving patients is not reported. With a multidisciplinary translational approach, we studied EVs from the blood of 33 patients with moderate-to-severe ARDS. The EVs were isolated from the blood of ARDS and control subjects. Immunoblotting and magnetic beads immunoisolation complemented by standardized flow cytometry and nanoparticles tracking analyses identified in the ARDS patients a subset of EVs with mesenchymal stem cell (MSC) origin (CD73+CD105+Cd34-CD45-). These EVs have 4.7-fold greater counts compared to controls and comprise the transforming growth factor-beta receptor I (TβRI)/Alk5 and the Runx1 transcription factor. Time course analyses showed that the expression pattern of two Runx1 isoforms is critical for ARDS outcome: the p52 isoform shows a continuous expression, while the p66 is short-lived. A high ratio Runx1p66/p52 provided a survival advantage, regardless of age, sex, disease severity or length of stay in the intensive care unit. Moreover, the Runx1p66 isoform is transiently expressed by cultured human bone marrow-derived MSCs, it is released in the EVs recoverable from the conditioned media and stimulates the proliferation of lipopolysaccharide (LPS)-treated ECs. The findings are consistent with a causal effect of Runx1p66 expression on EC proliferation. Furthermore, morphological and functional assays showed that the EVs bearing the Runx1p66 enhanced junctional integrity of LPS-injured ECs and decreased lung histological severity in the LPS-treated mice. The expression pattern of Runx1 isoforms might be a reliable circulatory biomarker of ARDS activity and a novel determinant of the molecular mechanism for lung vascular/tissue repair and recovery after severe injury. |
Mendeley readers
The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 37 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 8 | 22% |
| Researcher | 6 | 16% |
| Student > Doctoral Student | 4 | 11% |
| Student > Bachelor | 3 | 8% |
| Student > Master | 3 | 8% |
| Other | 3 | 8% |
| Unknown | 10 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 8 | 22% |
| Agricultural and Biological Sciences | 7 | 19% |
| Biochemistry, Genetics and Molecular Biology | 2 | 5% |
| Neuroscience | 2 | 5% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
| Other | 4 | 11% |
| Unknown | 13 | 35% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. 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 29 August 2023.
All research outputs
#8,538,940
of 25,385,509 outputs
Outputs from Clinical and Translational Medicine
#337
of 1,060 outputs
Outputs of similar age
#137,613
of 342,290 outputs
Outputs of similar age from Clinical and Translational Medicine
#5
of 9 outputs
Altmetric has tracked 25,385,509 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,060 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.2. This one has gotten more attention than average, scoring higher than 66% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 342,290 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.
We're also able to compare this research output to 9 others from the same source and published within six weeks on either side of this one. This one has scored higher than 4 of them.