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Role of endothelial microRNA 155 on capillary leakage in systemic inflammation

Overview of attention for article published in Critical Care, February 2021
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Title
Role of endothelial microRNA 155 on capillary leakage in systemic inflammation
Published in
Critical Care, February 2021
DOI 10.1186/s13054-021-03500-0
Pubmed ID
Authors

Valerie Etzrodt, Temitayo O. Idowu, Heiko Schenk, Benjamin Seeliger, Antje Prasse, Kristina Thamm, Thorben Pape, Janina Müller-Deile, Matijs van Meurs, Thomas Thum, Ankita Garg, Robert Geffers, Klaus Stahl, Samir M. Parikh, Hermann Haller, Sascha David

Abstract

Capillary leakage is a key contributor to the pathological host response to infections. The underlying mechanisms remain incompletely understood, and the role of microRNAs (MIR) has not been investigated in detail. We hypothesized that specific MIRs might be regulated directly in the endothelium thereby contributing to vascular leakage. SmallRNA sequencing of endotoxemic murine pulmonary endothelial cells (ECs) was done to detect regulated vascular MIRs. In vivo models: transgenic zebrafish (flk1:mCherry/l-fabp:eGFP-DPB), knockout/wildtype mouse (B6.Cg-Mir155tm1.1Rsky/J); disease models: LPS 17.5 mg/kgBW and cecal ligation and puncture (CLP); in vitro models: stimulated human umbilical vein EC (HUVECs), transendothelial electrical resistance. Endothelial MIR155 was identified as a promising candidate in endotoxemic murine pulmonary ECs (25 × upregulation). Experimental overexpression in a transgenic zebrafish line and in HUVECs was sufficient to induce spontaneous vascular leakage. To the contrary, genetic MIR155 reduction protects against permeability both in vitro and in endotoxemia in vivo in MIR155 heterozygote knockout mice thereby improving survival by 40%. A tight junction protein, Claudin-1, was down-regulated both in endotoxemia and by experimental MIR155 overexpression. Translationally, MIR155 was detectable at high levels in bronchoalveolar fluid of patients with ARDS compared to healthy human subjects. We found that MIR155 is upregulated in the endothelium in mouse and men as part of a systemic inflammatory response and might contribute to the pathophysiology of vascular leakage in a Claudin-1-dependent manner. Future studies have to clarify whether MIR155 could be a potential therapeutic target.

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The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 23 100%

Demographic breakdown

Readers by professional status Count As %
Student > Doctoral Student 3 13%
Researcher 3 13%
Student > Ph. D. Student 3 13%
Librarian 2 9%
Student > Bachelor 1 4%
Other 2 9%
Unknown 9 39%
Readers by discipline Count As %
Medicine and Dentistry 9 39%
Agricultural and Biological Sciences 2 9%
Biochemistry, Genetics and Molecular Biology 1 4%
Immunology and Microbiology 1 4%
Engineering 1 4%
Other 0 0%
Unknown 9 39%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 22 February 2021.
All research outputs
#14,048,680
of 23,283,373 outputs
Outputs from Critical Care
#4,721
of 6,133 outputs
Outputs of similar age
#214,597
of 418,099 outputs
Outputs of similar age from Critical Care
#89
of 107 outputs
Altmetric has tracked 23,283,373 research outputs across all sources so far. This one is in the 38th percentile – i.e., 38% of other outputs scored the same or lower than it.
So far Altmetric has tracked 6,133 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 19.6. This one is in the 22nd percentile – i.e., 22% of its peers scored the same or lower than it.
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 418,099 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 47th percentile – i.e., 47% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 107 others from the same source and published within six weeks on either side of this one. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.