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IRE1α inhibition decreased TXNIP/NLRP3 inflammasome activation through miR-17-5p after neonatal hypoxic–ischemic brain injury in rats

Overview of attention for article published in Journal of Neuroinflammation, February 2018
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  • Above-average Attention Score compared to outputs of the same age (58th percentile)

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Citations

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Title
IRE1α inhibition decreased TXNIP/NLRP3 inflammasome activation through miR-17-5p after neonatal hypoxic–ischemic brain injury in rats
Published in
Journal of Neuroinflammation, February 2018
DOI 10.1186/s12974-018-1077-9
Pubmed ID
Authors

Di Chen, Brandon J. Dixon, Desislava M. Doycheva, Bo Li, Yang Zhang, Qin Hu, Yue He, Zongduo Guo, Derek Nowrangi, Jerry Flores, Valery Filippov, John H. Zhang, Jiping Tang

Abstract

The endoplasmic reticulum (ER) is responsible for the control of correct protein folding and protein function which is crucial for cell survival. However, under pathological conditions, such as hypoxia-ischemia (HI), there is an accumulation of unfolded proteins thereby triggering the unfolded protein response (UPR) and causing ER stress which is associated with activation of several stress sensor signaling pathways, one of them being the inositol requiring enzyme-1 alpha (IRE1α) signaling pathway. The UPR is regarded as a potential contributor to neuronal cell death and inflammation after HI. In the present study, we sought to investigate whether microRNA-17 (miR-17), a potential IRE1α ribonuclease (RNase) substrate, arbitrates downregulation of thioredoxin-interacting protein (TXNIP) and consequent NLRP3 inflammasome activation in the immature brain after HI injury and whether inhibition of IRE1α may attenuate inflammation via miR-17/TXNIP regulation. Postnatal day 10 rat pups (n = 287) were subjected to unilateral carotid artery ligation followed by 2.5 h of hypoxia (8% O2). STF-083010, an IRE1α RNase inhibitor, was intranasally delivered at 1 h post-HI or followed by an additional one administration per day for 2 days. MiR-17-5p mimic or anti-miR-17-5p inhibitor was injected intracerebroventricularly at 48 h before HI. Infarct volume and body weight were used to evaluate the short-term effects while brain weight, gross and microscopic brain tissue morphologies, and neurobehavioral tests were conducted for the long-term evaluation. Western blots, immunofluorescence staining, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), and co-immunoprecipitation (Co-IP) were used for mechanism studies. Endogenous phosphorylated IRE1α expression was significantly increased after HI. Intranasal administration of STF-083010 alleviated brain injury and improved neurological behavior. MiR-17-5p expression was reduced after HI, and this decrease was attenuated by STF-083010 treatment. MiR-17-5p mimic administration ameliorated TXNIP expression, NLRP3 inflammasome activation, caspase-1 cleavage, and IL-1β production, as well as brain infarct volume. Conversely, anti-miR-17-5p inhibitor reversed IRE1α inhibition-induced decrease in TXNIP expression and inflammasome activation, as well as exacerbated brain injury after HI. IRE1a-induced UPR pathway may contribute to inflammatory activation and brain injury following neonatal HI. IRE1a activation, through decay of miR-17-5p, elevated TXNIP expression to activate NLRP3 inflammasome and aggravated brain damage.

Twitter Demographics

The data shown below were collected from the profiles of 5 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 45 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 18%
Researcher 6 13%
Student > Master 6 13%
Student > Bachelor 4 9%
Student > Doctoral Student 3 7%
Other 11 24%
Unknown 7 16%
Readers by discipline Count As %
Medicine and Dentistry 10 22%
Neuroscience 8 18%
Biochemistry, Genetics and Molecular Biology 7 16%
Psychology 5 11%
Immunology and Microbiology 3 7%
Other 6 13%
Unknown 6 13%

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 09 May 2019.
All research outputs
#7,911,568
of 14,983,043 outputs
Outputs from Journal of Neuroinflammation
#774
of 1,811 outputs
Outputs of similar age
#146,061
of 360,953 outputs
Outputs of similar age from Journal of Neuroinflammation
#2
of 3 outputs
Altmetric has tracked 14,983,043 research outputs across all sources so far. This one is in the 46th percentile – i.e., 46% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,811 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.6. This one has gotten more attention than average, scoring higher than 56% 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 360,953 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 58% of its contemporaries.
We're also able to compare this research output to 3 others from the same source and published within six weeks on either side of this one.