| Title |
Targeting the PXR–TLR4 signaling pathway to reduce intestinal inflammation in an experimental model of necrotizing enterocolitis
|
|---|---|
| Published in |
Pediatric Research, February 2018
|
| DOI | 10.1038/pr.2018.14 |
| Pubmed ID | |
| Authors |
Kezhen Huang, Subhajit Mukherjee, Vera DesMarais, Joseph M Albanese, Ektor Rafti, Andrew Draghi II, Leigh A Maher, Kamal M Khanna, Sridhar Mani, Adam P Matson |
| Abstract |
There is substantial evidence that signaling through Toll-like receptor 4 (TLR4) contributes to the pathogenesis of necrotizing enterocolitis (NEC). Pregnane X receptor (PXR), a xenobiotic sensor and signaling intermediate for certain host-bacterial metabolites, has been shown to negatively regulate TLR4 signaling. Here we investigated the relationship between PXR and TLR4 in the developing murine intestine and explored the capacity of PXR to modulate inflammatory pathways involved in experimental NEC. Wild-type and PXR-/- mice were studied at various time points of development in an experimental model of NEC. In addition, we studied the ability of the secondary bile acid lithocholic acid (LCA), a known PXR agonist in liver, to activate intestinal PXR and reduce NEC-related intestinal inflammation. We found a reciprocal relationship between the developmental expression of PXR and TLR4 in wild-type murine intestine, with PXR acting to reduce TLR4 expression by decreasing TLR4 mRNA stability. In addition, PXR-/- mice exhibited a remarkably heightened severity of disease in experimental NEC. Moreover, LCA attenuated intestinal proinflammatory responses in the early stages of experimental NEC. These findings provide proactive insights into the regulation of TLR4 in the developing intestine. Targeting PXR may be a novel approach for NEC prevention.Pediatric Research accepted article preview online, 23 January 2018. doi:10.1038/pr.2018.14. |
X Demographics
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.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 39 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 15% |
| Researcher | 6 | 15% |
| Student > Bachelor | 5 | 13% |
| Other | 4 | 10% |
| Student > Master | 3 | 8% |
| Other | 3 | 8% |
| Unknown | 12 | 31% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 6 | 15% |
| Agricultural and Biological Sciences | 5 | 13% |
| Biochemistry, Genetics and Molecular Biology | 4 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 8% |
| Immunology and Microbiology | 3 | 8% |
| Other | 4 | 10% |
| Unknown | 14 | 36% |
Attention Score in Context
This research output has an Altmetric Attention Score of 9. 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 07 March 2018.
All research outputs
#3,777,768
of 23,018,998 outputs
Outputs from Pediatric Research
#839
of 5,116 outputs
Outputs of similar age
#75,524
of 331,219 outputs
Outputs of similar age from Pediatric Research
#4
of 46 outputs
Altmetric has tracked 23,018,998 research outputs across all sources so far. Compared to these this one has done well and is in the 83rd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,116 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.6. This one has done well, scoring higher than 83% 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 331,219 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 76% of its contemporaries.
We're also able to compare this research output to 46 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 91% of its contemporaries.