Evidence map›Paper›PMID 40685360›Full record

ArticleMilitary Medical Research2025

Glucocorticoids trigger muscle-liver crosstalk to attenuate acute liver injury and promote liver regeneration via the FGF6-FGFBP1 axis.

Yue-Jie Xu, Cai-Zhi Liu, Ying Chen, Lan-Xin Li, Bo Xu, Ling-Xin You, Mei-Yao Meng, Xin Li, Hong Zhang, Qiu-Rong Ding and 4 more

Abstract read
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In one paragraph

Article in Military Medical Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
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

14 authors.

Yue-Jie Xu *Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Cai-Zhi Liu *Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China. adaica@sjtu.edu.cn.
Ying ChenJinzhou Medical University Graduate Training Base (Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine), Jinzhou, 121001, Liaoning, China.
Lan-Xin LiDepartment of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Bo XuDepartment of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Ling-Xin YouDepartment of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Mei-Yao MengShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Xin LiResearch Direction of New Microecological Technology, Jinan Microecological Biomedicine Shandong Laboratory, Jinan, 250000, China.
Hong ZhangDepartment of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Qiu-Rong DingCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Rong ZhangDepartment of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Xin-Ran MaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Xiao-Hua ChenDepartment of Infectious Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China. chenxiaohua2000@163.com.
Cheng HuDepartment of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China. alfredhc@sjtu.edu.cn.ORCID 0000-0003-4314-2386

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAcute liver injury (ALI) requires rapid hepatic regeneration to avert fatal liver failure. As key mechanisms, systemic metabolic remodeling and inter-organ crosstalk are critical for this regenerative process. Skeletal muscle, as a major metabolic organ system, undergoes significant remodeling during ALI. However, its specific regulatory contributions remain largely uncharacterized.

methodsPartial (2/3) hepatectomy and acetaminophen were used to induce ALI in male mice. RNA-sequencing (RNA-seq), assay for transposase-accessible chromatin by sequencing (ATAC-seq), chromatin immunoprecipitation, luciferase assay, Western blotting, TUNEL assay, immunohistochemistry, and phase separation assays were performed to reveal the transcriptional axis involved. Serum fibroblast growth factor binding protein 1 (FGFBP1) protein levels in ALI patients were assessed via enzyme-linked immunosorbent assay.

resultsIntegrated analysis of RNA-seq and ATAC-seq following ALI identifies glucocorticoid (GC) signaling-mediated regulation of fibroblast growth factor 6 (FGF6) in skeletal muscle metabolism. Muscle-specific knockdown of GC receptor (GR) exacerbates ALI and suppresses liver regeneration. Fgf6-knockout mice exhibited improved ALI and enhanced liver regeneration, with intramuscular injection of FGF6-neutralizing antibody rescuing the detrimental effects induced by GR knockdown. Further analysis of the FGF6 downstream target revealed that FGF6 regulates FGFBP1 expression through extracellular signal regulated kinase-activating transcription factor 3 signaling. Moreover, FGF6 regulates the heparin-dependent release kinetics of FGFBP1 by perturbing its liquid-liquid phase separation (LLPS)-driven condensate dynamics at the plasma membrane. Circulating FGFBP1 subsequently interacts with hepatic fibroblast growth factor 5 (FGF5) through LLPS mechanisms to regulate liver regeneration.

conclusionOur results demonstrate a molecular mechanism by which muscle-liver crosstalk can initiate and sustain liver regeneration via the FGF6-FGFBP1/FGF5 axis, providing a potential therapeutic target and treatment strategy for ALI.

Indexed as

GlucocorticoidsLiverLiver RegenerationMuscle, SkeletalAnimalsHumansMaleMiceMice, Inbred C57BLSignal TransductionGlucocorticoidsAcute liver injury (ALI)Fibroblast growth factor 6 (FGF6)Fibroblast growth factor binding protein 1 (FGFBP1)Liver regenerationSkeletal muscle

Identifiers

PMID40685360
PMCPMC12278513

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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.