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TREM-1 triggers necroptosis of macrophages through mTOR-dependent mitochondrial fission during acute lung injury

Overview of attention for article published in Journal of Translational Medicine, March 2023
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Title
TREM-1 triggers necroptosis of macrophages through mTOR-dependent mitochondrial fission during acute lung injury
Published in
Journal of Translational Medicine, March 2023
DOI 10.1186/s12967-023-04027-4
Pubmed ID
Authors

Wen-Jing Zhong, Jun Zhang, Jia-Xi Duan, Chen-Yu Zhang, Sheng-Chao Ma, Yu-Sheng Li, Nan-Shi-Yu Yang, Hui-Hui Yang, Jian-Bing Xiong, Cha-Xiang Guan, Zhi-Xing Jiang, Zhi-Jian You, Yong Zhou

Abstract

Necroptosis of macrophages is a necessary element in reinforcing intrapulmonary inflammation during acute lung injury (ALI). However, the molecular mechanism that sparks macrophage necroptosis is still unclear. Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor expressed broadly on monocytes/macrophages. The influence of TREM-1 on the destiny of macrophages in ALI requires further investigation. TREM-1 decoy receptor LR12 was used to evaluate whether the TREM-1 activation induced necroptosis of macrophages in lipopolysaccharide (LPS)-induced ALI in mice. Then we used an agonist anti-TREM-1 Ab (Mab1187) to activate TREM-1 in vitro. Macrophages were treated with GSK872 (a RIPK3 inhibitor), Mdivi-1 (a DRP1 inhibitor), or Rapamycin (an mTOR inhibitor) to investigate whether TREM-1 could induce necroptosis in macrophages, and the mechanism of this process. We first observed that the blockade of TREM-1 attenuated alveolar macrophage (AlvMs) necroptosis in mice with LPS-induced ALI. In vitro, TREM-1 activation induced necroptosis of macrophages. mTOR has been previously linked to macrophage polarization and migration. We discovered that mTOR had a previously unrecognized function in modulating TREM-1-mediated mitochondrial fission, mitophagy, and necroptosis. Moreover, TREM-1 activation promoted DRP1Ser616 phosphorylation through mTOR signaling, which in turn caused surplus mitochondrial fission-mediated necroptosis of macrophages, consequently exacerbating ALI. In this study, we reported that TREM-1 acted as a necroptotic stimulus of AlvMs, fueling inflammation and aggravating ALI. We also provided compelling evidence suggesting that mTOR-dependent mitochondrial fission is the underpinning of TREM-1-triggered necroptosis and inflammation. Therefore, regulation of necroptosis by targeting TREM-1 may provide a new therapeutic target for ALI in the future.

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Mendeley readers

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The data shown below were compiled from readership statistics for 9 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 9 100%

Demographic breakdown

Readers by professional status Count As %
Librarian 2 22%
Unspecified 1 11%
Student > Doctoral Student 1 11%
Unknown 5 56%
Readers by discipline Count As %
Arts and Humanities 1 11%
Unspecified 1 11%
Biochemistry, Genetics and Molecular Biology 1 11%
Immunology and Microbiology 1 11%
Unknown 5 56%
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 07 March 2023.
All research outputs
#15,824,506
of 23,504,445 outputs
Outputs from Journal of Translational Medicine
#2,343
of 4,163 outputs
Outputs of similar age
#180,823
of 339,661 outputs
Outputs of similar age from Journal of Translational Medicine
#73
of 130 outputs
Altmetric has tracked 23,504,445 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,163 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.6. This one is in the 31st percentile – i.e., 31% 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 339,661 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 130 others from the same source and published within six weeks on either side of this one. This one is in the 29th percentile – i.e., 29% of its contemporaries scored the same or lower than it.