Evidence map›Paper›PMID 41417477›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

F13A1-Mediated Macrophage Activation Promotes MASH Progression via the PKM2/HIF1A Pathway.

Qianrang Lu, Meiching Ong, Xuewen Yi, Muqiong Xing, Xinyao Tian, Ke Zhang, Ling Lu, Hao Wang, Xiaohan Lin, Jun Fang and 7 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. 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

17 authors.

Qianrang LuDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Meiching OngDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Xuewen YiDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Muqiong XingState Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Xinyao TianDepartment of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Ke ZhangDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Ling LuJiangsu Key Laboratory of Organ Transplantation and Transplant Immunology, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Hepatobiliary Center, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Hao WangHepatobiliary Center, The First Affiliated Hospital, Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, Jiangsu, China.
Xiaohan LinDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jun FangDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Aibo MuDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jiaying CaoDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jingyu JiangDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Feng GaoDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Hongjun LiState Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Baohong WangState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Qi LingDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.ORCID https://orcid.org/0000-0002-7377-2381

Funding

"Leading Goose" R&D Program of Zhejiang Province 2024C03168National Natural Science Foundation of China 82170668National Natural Science Foundation of China 82241215National Natural Science Foundation of China 82572036
6 · The paper itself

Abstract

Macrophages are central mediators of hepatic inflammation and fibrosis in metabolic-associated steatohepatitis (MASH), yet the mechanisms driving their activation remain unclear. Integration of four human single-nucleus transcriptomic datasets identified Coagulation Factor XIII-A (F13A1)-positive macrophages as the predominant subset in MASH livers, a finding validated in patient samples and murine models. Lipid-stressed hepatocytes induce F13A1 expression through a sphingosine-1-phosphate (S1P)-dependent mechanism. Silencing F13A1 suppressed the pro-inflammatory phenotype and alleviated hepatic injury in vivo. Mechanistically, F13A1 directly interacted with pyruvate kinase M2 (PKM2), promoting its dimerization, a process enhanced by intracellular calcium levels. Dimerized PKM2 translocated into the nucleus and upregulates interleukin-1 beta (IL1B) expression via the PKM2/HIF1A (Hypoxia-inducible factor 1-alpha) axis. In addition, F13A1 enhanced the Warburg effect in macrophages through PKM2-mediated metabolic reprogramming. Pharmacologic activation of PKM2 with DASA-58 abrogated F13A1-driven inflammation, and PEG-PLA micelle-mediated delivery of DASA-58 ameliorated hepatic inflammation in vivo. These findings establish F13A1 as a critical driver of macrophage-mediated inflammation in MASH and highlight the F13A1/PKM2/HIF1A pathway as a promising therapeutic target.

Indexed as

Carrier ProteinsHypoxia-Inducible Factor 1, alpha SubunitMacrophage ActivationMembrane ProteinsNon-alcoholic Fatty Liver DiseasePyruvate KinaseThyroid HormonesAnimalsDisease Models, AnimalDisease ProgressionHumansLiverMacrophagesMaleMiceMice, Inbred C57BLCarrier ProteinsHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitMembrane ProteinsPkm protein, mousePyruvate KinaseThyroid Hormone-Binding ProteinsThyroid Hormonesfactor XIIIHIF1Amacrophage activationMASHPKM2

Identifiers

PMID41417477
PMCPMC12955996

What Socratic holds

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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 Socratic graph.