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NLR Family Pyrin Domain‐Containing 3 Inflammasome Activation in Hepatic Stellate Cells Induces Liver Fibrosis in Mice

Overview of attention for article published in Hepatology, February 2019
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Title
NLR Family Pyrin Domain‐Containing 3 Inflammasome Activation in Hepatic Stellate Cells Induces Liver Fibrosis in Mice
Published in
Hepatology, February 2019
DOI 10.1002/hep.30252
Pubmed ID
Authors

Maria Eugenia Inzaugarat, Casey D. Johnson, Theresa Maria Holtmann, Matthew D. McGeough, Christian Trautwein, Bettina G. Papouchado, Robert Schwabe, Hal M. Hoffman, Alexander Wree, Ariel E. Feldstein

Abstract

The NLRP3 inflammasome plays an important role in liver fibrosis development. However, the mechanisms involved in NLRP3-induced fibrosis are unclear. Our aim was to test the hypothesis that the NLRP3 inflammasome in hepatic stellate cells (HSC) can directly regulate their activation and contribute to liver fibrosis. Primary HSC isolated from WT, Nlrp3-/- , or Nlrp3L351PneoR knock-in crossed to inducible (estrogen receptor Cre - CreT) mice were incubated with LPS and ATP, or 4OH-tamoxifen, respectively. HSC-specific Nlrp3L351P -knock-in mice were generated by crossing transgenic mice expressing lecithin retinol acyltransferase (Lrat)-driven Cre and maintained on standard rodent chow for 6 months. Mice were then sacrificed; liver tissue and serum were harvested. Nlrp3 inflammasome activation along with HSC phenotype and fibrosis were assessed by RT-PCR, Western blot, FACS, ELISA, immunofluorescence and immunohistochemistry. Stimulated WT HSC displayed increased levels of NLRP3 inflammasome-induced ROS production and Cathepsin B activity, accompanied by an upregulation of mRNA and protein levels of fibrotic makers, an effect abrogated in Nlrp3-/- HSC. Nlrp3L351P CreT HSC also showed elevated mRNA and protein expression of fibrotic markers 24h after inflammasome activation induced with 4OH-tamoxifen. Protein and mRNA expression levels of fibrotic markers were also found to be increased in isolated HSC and whole liver tissue from Nlrp3L351P Lrat Cre mice compared to WT. Liver sections from 24 week-old NlrpL351P Lrat Cre mice showed fibrotic changes with increased αSMA and desmin positive cells and collagen deposition, independent of inflammatory infiltrates; these changes were also observed after LPS challenge in 8 week-old NlrpL351P Lrat Cre mice. Conclusion Our results highlight a direct role for the NLRP3 inflammasome in the activation of HSC directly triggering liver fibrosis. This article is protected by copyright. All rights reserved.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 38 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 13%
Researcher 4 11%
Student > Bachelor 3 8%
Professor 2 5%
Student > Master 2 5%
Other 5 13%
Unknown 17 45%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 18%
Agricultural and Biological Sciences 3 8%
Unspecified 2 5%
Medicine and Dentistry 2 5%
Environmental Science 1 3%
Other 2 5%
Unknown 21 55%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 18 September 2018.
All research outputs
#19,954,338
of 25,385,509 outputs
Outputs from Hepatology
#7,899
of 9,093 outputs
Outputs of similar age
#321,947
of 447,265 outputs
Outputs of similar age from Hepatology
#72
of 94 outputs
Altmetric has tracked 25,385,509 research outputs across all sources so far. This one is in the 18th percentile – i.e., 18% of other outputs scored the same or lower than it.
So far Altmetric has tracked 9,093 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.4. This one is in the 10th percentile – i.e., 10% 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 447,265 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 94 others from the same source and published within six weeks on either side of this one. This one is in the 18th percentile – i.e., 18% of its contemporaries scored the same or lower than it.