Evidence map›Paper›PMID 41540461›Full record

ArticleCell communication and signaling : CCS2026

Lactate attenuates hepatic ischemia-reperfusion injury by reducing intrahepatic inflammation and suppressing hepatocyte-neutrophil interaction via the IL-33/ST2 pathway.

Peiyang Fang, Zihan Zhang, Jingjing Zhu, Haozhe Xu, Xiaotong Han, Nan Xu, Xiyu Wang, Longyang Zhou, Xiaonan Du, Hua Jin and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell communication and signaling : CCS, 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

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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
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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.

Peiyang Fang *Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
Zihan Zhang *Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
Jingjing ZhuMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
Haozhe XuMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
Xiaotong HanMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
Nan XuMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
Xiyu WangMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
Longyang ZhouMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
Xiaonan DuMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
Hua JinMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
Dong ZhangMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China. zhangd@ccmu.edu.cn.
Guangyong SunMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China. sungy@ccmu.edu.cn.

Funding

Grants from the National Natural Science Foundation of China 82200635Grants from the National Natural Science Foundation of China 82270606Grants from the National Natural Science Foundation of China 82370578Natural Science Foundation of Beijing Municipality No. 7232034the Youth Beijing Scholar No. 035
6 · The paper itself

Abstract

backgroundHepatic ischemia-reperfusion injury (HIRI) is a critical contributor to adverse clinical outcomes and increased mortality after liver surgery or transplantation. Lactate, formerly regarded as a metabolic waste product, has emerged as a critical immunomodulatory molecule. This study investigated how lactate modulates HIRI by regulating intrahepatic inflammation and intercellular communication.

methodsA mouse model of HIRI was constructed, along with in vitro hypoxia/reoxygenation (H/R) of primary hepatocytes and LPS-stimulated bone marrow-derived neutrophils, to evaluate the protective effects of sodium lactate. RNA sequencing was performed to identify changes in transcriptional profiles induced by lactate pretreatment and to explore regulatory mechanisms involving hepatocytes and neutrophils during HIRI. Cell-cell interaction analysis was performed to identify key interactions by which lactate regulates hepatocyte-neutrophil communication. Furthermore, analysis of transcription factor binding motifs using the JASPAR database was conducted to elucidate potential molecular mechanisms underlying the previously identified key interactions.

resultsLactate administration significantly alleviated hepatic inflammation and tissue injury in HIRI mice. Transcriptomic analysis revealed that lactate attenuated hepatocyte-mediated inflammatory responses, chemotaxis, and apoptosis, while also suppressing neutrophil-driven inflammation, migration, oxidative stress, and NET formation. Integrated digital spatial profiling (DSP) combined with cell-cell interaction analysis revealed IL-33/ST2 as a critical ligand-receptor pair mediating hepatocyte-neutrophil crosstalk, which was significantly downregulated by lactate. IL-33 has been demonstrated to stimulate neutrophil activation and exacerbate liver inflammation via its receptor ST2 in HIRI. Consistently, lactate pretreatment suppressed this pathway, thereby mitigating hepatic injury and intrahepatic inflammation. Mechanistically, lactate inhibited IL-33 expression in hepatocytes via the AKT/c-Fos signaling axis and reduced ST2 expression in neutrophils through the JAK/STAT3 pathway.

conclusionsLactate alleviates HIRI by protecting hepatocytes, suppressing neutrophil-driven inflammation, and disrupting hepatocyte-neutrophil communication through the IL-33/ST2 axis.

Indexed as

Cell CommunicationHepatocytesInflammationInterleukin-1 Receptor-Like 1 ProteinInterleukin-33Lactic AcidLiverNeutrophilsReperfusion InjurySignal TransductionAnimalsMaleMiceMice, Inbred C57BLIl1rl1 protein, mouseIl33 protein, mouseInterleukin-1 Receptor-Like 1 ProteinInterleukin-33Lactic AcidCell communicationHepatic ischemia-reperfusionHepatocyteIL-33/ST2LactateNeutrophil

Identifiers

PMID41540461
PMCPMC12895952

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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.