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Spermine Alleviates Acute Liver Injury by Inhibiting Liver-Resident Macrophage Pro-Inflammatory Response Through ATG5-Dependent Autophagy

Overview of attention for article published in Frontiers in immunology, May 2018
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Title
Spermine Alleviates Acute Liver Injury by Inhibiting Liver-Resident Macrophage Pro-Inflammatory Response Through ATG5-Dependent Autophagy
Published in
Frontiers in immunology, May 2018
DOI 10.3389/fimmu.2018.00948
Pubmed ID
Authors

Shun Zhou, Jian Gu, Rui Liu, Song Wei, Qi Wang, Hongbing Shen, Yifan Dai, Haoming Zhou, Feng Zhang, Ling Lu

Abstract

Liver-resident macrophages (Kupffer cells, KCs) and autophagy play critical roles in the pathogenesis of toxin-induced liver injury. Recent evidence indicates that autophagy can regulate macrophage M1/M2 polarization under different inflammatory conditions. Polyamines, including putrescine, spermidine, and spermine (SPM), are polycations with anti-oxidative, anti-aging, and cell autophagy induction properties. This study aimed to determine the mechanisms by which SPM protects against thioacetamide (TAA)-induced acute liver injury in a mouse model. Pretreatment with SPM significantly alleviated liver injury and reduced intrahepatic inflammation in TAA-induced liver injury compared to controls. SPM markedly inhibited M1 polarization, but promoted M2 polarization of KCs obtained from TAA-exposed livers, as evidenced by decreased IL-1β and iNOS gene induction but increased Arg-1 and Mrc-1 gene induction accompanied by decreased STAT1 activation and increased STAT6 activation. Furthermore, pretreatment with SPM enhanced autophagy, as revealed by increased LC3B-II levels, decreased p62 protein expression, and increased ATG5 protein expression in TAA-treated KCs. Knockdown of ATG5 in SPM-pretreated KCs by siRNA resulted in a significant increase in pro-inflammatory TNF-α and IL-6 secretion and decreased anti-inflammatory IL-10 secretion after TAA treatment, while no significant changes were observed in cytokine production in the TAA treatment alone. Additionally, the effect of SPM on regulation of KC M1/M2 polarization was abolished by ATG5 knockdown in TAA-exposed KCs. Finally, in vivo ATG5 knockdown in KCs abrogated the protective effect of SPM against TAA-induced acute liver injury. Our results indicate that SPM-mediated autophagy inhibits M1 polarization, while promoting M2 polarization of KCs in TAA-treated livers via upregulation of ATG5 expression, leading to attenuated liver injury. This study provides a novel target for the prevention of acute liver injury.

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Mendeley readers

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The data shown below were compiled from readership statistics for 51 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 51 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 20%
Student > Master 6 12%
Researcher 4 8%
Student > Doctoral Student 3 6%
Student > Postgraduate 3 6%
Other 9 18%
Unknown 16 31%
Readers by discipline Count As %
Medicine and Dentistry 9 18%
Immunology and Microbiology 8 16%
Biochemistry, Genetics and Molecular Biology 6 12%
Agricultural and Biological Sciences 4 8%
Computer Science 1 2%
Other 8 16%
Unknown 15 29%
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 May 2018.
All research outputs
#22,767,715
of 25,382,440 outputs
Outputs from Frontiers in immunology
#27,437
of 31,537 outputs
Outputs of similar age
#298,629
of 338,899 outputs
Outputs of similar age from Frontiers in immunology
#649
of 711 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 31,537 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one is in the 1st percentile – i.e., 1% 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 338,899 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 711 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.