Evidence map›Paper›PMID 32666684›Full record

ArticleAging cell2020

Aging aggravated liver ischemia and reperfusion injury by promoting STING-mediated NLRP3 activation in macrophages.

Weizhe Zhong, Zhuqing Rao, Jianhua Rao, Guoyong Han, Ping Wang, Tao Jiang, Xiongxiong Pan, Shun Zhou, Haoming Zhou, Xuehao Wang

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Aging cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 1 pooled it
5.1field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

86 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 citations in OpenAlex.

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26 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Weizhe ZhongHepatobiliary/Liver Transplantation Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Zhuqing RaoDepartment of Anesthesiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Jianhua RaoHepatobiliary/Liver Transplantation Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Guoyong HanHepatobiliary/Liver Transplantation Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Ping WangHepatobiliary/Liver Transplantation Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Tao JiangHepatobiliary/Liver Transplantation Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Xiongxiong PanDepartment of Anesthesiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Shun ZhouHepatobiliary/Liver Transplantation Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Haoming ZhouHepatobiliary/Liver Transplantation Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Xuehao WangHepatobiliary/Liver Transplantation Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.ORCID 0000-0001-5849-0098
Chinese Academy of Medical Sciences & Peking Union Medical College · CNNanjing Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although aggravated liver injury has been reported in aged livers post-ischemia and reperfusion (IR), the underlying mechanism of innate immune activation of aged macrophages is not well understood. Here, we investigated whether and how Stimulator of interferon genes (STING) signaling regulated macrophage proinflammatory activation and liver IR injury. Mice were subjected to hepatic IR in vivo. Macrophages isolated from IR-stressed livers and bone marrow-derived macrophages (BMDMs) from young and aged mice were used for in vitro studies. Enhanced nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3) activation was found in both livers and macrophages of aged mice post-IR. NLRP3 knockdown in macrophages inhibited intrahepatic inflammation and liver injury in both young and aged mice. Interestingly, enhanced activation of the STING/ TANK-binding kinase 1 (TBK1) signaling pathway was observed in aged macrophages post-IR and mitochondria DNA (mtDNA) stimulation. STING suppression blocked over-activation of NLRP3 signaling and excessive secretion of proinflammatory cytokines/chemokines in the mtDNA-stimulated BMDMs from aged mice. More importantly, STING knockdown in macrophages abrogated the detrimental role of aging in aggravating liver IR injury and intrahepatic inflammation. Finally, peripheral blood from the recipients undergoing liver transplantation was collected and analyzed. The results showed that the elderly recipients had much higher levels of TNF-α, IL-6, IL-1β, and IL-18 post-transplantation, indicating increased NLRP3 activation in lR-stressed livers of elderly recipients. In summary, our study demonstrated that the STING-NLRP3 axis was critical for the proinflammatory response of aged macrophages and would be a novel therapeutic target to reduce IR injury in elderly patients.

Indexed as

Age FactorsAnimalsLiverMacrophagesMaleMembrane ProteinsMiceMice, Inbred C57BLNLR Family, Pyrin Domain-Containing 3 ProteinReperfusion InjurySTING ProteinMembrane ProteinsNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseSting1 protein, mouseSTING Proteinagingand reperfusion injuryleucine-rich repeat containing protein 3liver ischemiamacrophage immune responsenucleotide-binding domainstimulator of interferon genes

Identifiers

PMID32666684
PMCPMC7431827
OpenAlexW3042472931

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.