Evidence map›Paper›PMID 37422464›Full record

ArticleCell death discovery2023

Defective efferocytosis by aged macrophages promotes STING signaling mediated inflammatory liver injury.

Haoran Hu, Xuyu Cheng, Fei Li, Zhu Guan, Jian Xu, Dongming Wu, Yiyun Gao, Xinyu Zhan, Ping Wang, Haoming Zhou and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell death discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
11.8field-weighted citation impact, top 1% 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

50 citing papers in PubMed, 72 citations in OpenAlex.

  1. Article
  2. Innate immunity: current understandings and future perspectives.Signal transduction and targeted therapy · 2026
    Review
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  6. Review
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  9. Article
  10. Immune Aging as a Failure of Programmed Cell Death Coordination.International journal of molecular sciences · 2026
    Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Review
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  20. Review
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

12 authors at 2 institutions in 3 countries.

Haoran Hu *Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences; NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), 210029, Nanjing, Jiangsu Province, China.
Xuyu Cheng *Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, Jiangsu Province, China.
Fei LiDepartment of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, Jiangsu Province, China.
Zhu GuanDepartment of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, Jiangsu Province, China.
Jian XuHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences; NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), 210029, Nanjing, Jiangsu Province, China.
Dongming WuHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences; NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), 210029, Nanjing, Jiangsu Province, China.
Yiyun GaoHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences; NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), 210029, Nanjing, Jiangsu Province, China.
Xinyu ZhanHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences; NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), 210029, Nanjing, Jiangsu Province, China.
Ping WangHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences; NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), 210029, Nanjing, Jiangsu Province, China.
Haoming ZhouHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences; NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), 210029, Nanjing, Jiangsu Province, China. hmzhou@njmu.edu.cn.
Zhuqing RaoDepartment of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, Jiangsu Province, China. zhuqingraojsph@163.com.
Feng ChengHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences; NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), 210029, Nanjing, Jiangsu Province, China. docchengfeng@njmu.edu.cn.ORCID http://orcid.org/0000-0001-6131-2970
Academy of Medical Sciences · GBJiangsu Province Hospital · CN

Funding

Jiangsu Provincial Commission of Health and Family Planning ZD2021022
6 · The paper itself

Abstract

Aged livers have shown aggravated liver ischemia and reperfusion (IR) injury. Timely efferocytosis of apoptotic cells is a key mechanism for avoiding excessive inflammation and tissue injury. Here, we investigated the alteration of efferocytosis by aged macrophages and its role in regulating macrophage STING (stimulator of interferon genes) signaling and liver IR injury. Aged and young mice were subjected to liver partial IR model. Liver injury and inflammation were measured. Efferocytosis by aged macrophages and the underlying regulatory mechanism were analyzed as well. Aged macrophages exhibited impaired efferocytosis with decreased MerTK (c-mer proto-oncogene tyrosine kinase) activation, which was reversed by treatment of the MerTK CRISPR activation plasmid. Increased MerTK cleavage by ADAM17 (a disintegrin and metalloproteinase 17) due to enhanced ROS (reactive oxygen species) levels contributed to defective efferocytosis by aged macrophages. MerTK activation by suppressing ADAM17 or ROS improved aged macrophage efferocytosis, leading to reduced inflammatory liver injury. Moreover, increased apoptotic hepatocytes, DNA accumulation, and macrophage STING activation were observed in aged ischemic livers. Improvement in efferocytosis by aged macrophages via MerTK activation suppressed STING activation and inflammatory liver injury. Our study demonstrates that aging suppresses MerTK- mediated macrophage efferocytosis to promote macrophage STING activation and inflammatory liver IR injury, suggesting a new mechanism and potential therapy to promote inflammation resolution and efferocytosis in aged livers.

Identifiers

PMID37422464
PMCPMC10329662
OpenAlexW4383621788

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.