Evidence map›Paper›PMID 41196309›Full record

ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2025

PGC1α alleviates M1 macrophage polarization through dual regulation of succinate metabolism and TRAF5 expression to mitigate TLR4/NF-κB-driven inflammatory cascades and myocardial ischemia/reperfusion injury.

Jiajie Leng, Zhenrui Cao, Letai Li, Dingheng Hu, Yuxiang Luo, Bin Tu, Xiaoying Cao, Rui Tao, Yingjiu Jiang, Hongtao Tie

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Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
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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

10 authors.

Jiajie Leng *Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Zhenrui Cao *Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Letai Li *Chongqing Medical University, Chongqing, China.
Dingheng HuChongqing Medical University, Chongqing, China.
Yuxiang LuoDepartment of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Bin TuDepartment of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Xiaoying CaoDepartment of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Rui TaoWeight Management Center, Bishan Hospital, Chonqqing University of Chinese Medicine, Chongqing, China. taorui@vip.126.com.
Yingjiu JiangDepartment of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. jiangyinjiu@aliyun.com.
Hongtao TieDepartment of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. ht_tie@hospital.cqmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThis study investigates the dual regulatory role of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) in macrophage polarization and its therapeutic potential for mitigating myocardial ischemia/reperfusion injury (MI/RI).

methodsBy integrating in vivo murine myocardial MI/RI models with macrophage-specific genetic manipulation and multi-omics analyses, including transcriptomics, proteomics, and energy metabolomics, we comprehensively investigated the cardio-protective effects, immune regulation, and potential mechanism of PGC1α. Mechanistic validations were performed using macrophage hypoxia/reoxygenation models combined with gain- and loss-of-function experiments to elucidate the molecular interactions within the PGC1α-mediated signaling network.

resultsPGC1α emerged as a potential regulator of macrophage polarization through coordinated metabolic and protein regulation in MI/RI. It suppresses TLR4/NF-κB-driven inflammation via two prominent parallel pathways: (1) Metabolic control through SUCLG1/succinyl-CoA synthetase-mediated succinate generation; (2) negatively regulates protein by TRAF5 mRNA expression inhibition. This dual-axis regulation effectively dampens M1 macrophage polarization and pro-inflammatory cytokine storms. Furthermore, macrophage-specific PGC1α activation demonstrated cardio-protective effects by preserving cardiac function and reducing cardiomyocyte apoptosis.

conclusionOur findings established PGC1α as a potential regulator of macrophage polarization in MI/RI, bridging mitochondrial energy metabolism and protein expression with immune responses. The PGC1α-SUCLG1/succinate axis and PGC1α-TRAF5 axis unveil therapeutic targets and potential mechanisms for modulating inflammation in MI/RI. Future studies should focus on translating these mechanisms into clinical interventions through pharmacological PGC1α activation.

Indexed as

MacrophagesMyocardial Reperfusion InjuryPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaSuccinic AcidAnimalsInflammationMaleMiceMice, Inbred C57BLNF-kappa BSignal TransductionToll-Like Receptor 4NF-kappa BPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPpargc1a protein, mouseSuccinic AcidTlr4 protein, mouseToll-Like Receptor 4Immunometabolic crosstalkM1 macrophage polarizationMyocardial ischemia–reperfusion injuryPGC1αTLR4/NF-κB signaling

Identifiers

PMID41196309

What Socratic holds

Textmetadata
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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 Socratic graph.