Evidence map›Paper›PMID 40590856›Full record

ArticleHepatology (Baltimore, Md.)2026

MIF-mediated crosstalk between THRSP + hepatocytes and CD74 + lipid-associated macrophages in hepatic periportal zone drives MASH.

Xu Xu, Huagen Li, Hai Lin, Qichao Li, Yuenan Liu, Weijun Huang, Jundong Yang, Niannian Li, Zhenfei Gao, Shengming Wang and 8 more

Abstract read
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In one paragraph

Article in Hepatology (Baltimore, Md.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. The hepatic portal area in homeostasis and disease.Clinical and molecular hepatology · 2026
    Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Multiomics analysis reveals that senescent CXCL16Journal of translational medicine · 2026
    Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. 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

18 authors.

Xu XuDepartment of Otolaryngology Head and Neck Surgery, Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID 0000-0002-5854-6124
Huagen LiDepartment of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Hai LinWenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, China.
Qichao LiPostgraduate Training Base Alliance, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Yuenan LiuDepartment of Otolaryngology Head and Neck Surgery, Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Weijun HuangDepartment of Otolaryngology Head and Neck Surgery, Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jundong YangDepartment of Otolaryngology Head and Neck Surgery, Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Niannian LiDepartment of Otolaryngology Head and Neck Surgery, Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhenfei GaoDepartment of Otolaryngology Head and Neck Surgery, Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shengming WangDepartment of Otolaryngology Head and Neck Surgery, Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hangdong ShenDepartment of Otolaryngology Head and Neck Surgery, Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wenjun XueDepartment of Otolaryngology Head and Neck Surgery, Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Haolin YuanDepartment of Otolaryngology Head and Neck Surgery, Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wei WangDepartment of General Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jianwei ShuaiOujiang Laboratory (Zhejiang Laboratory for Regenerative Medicine, Vision and Brain Health), Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, China.
Junli LiuDepartment of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shankai YinDepartment of Otolaryngology Head and Neck Surgery, Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Feng LiuDepartment of Otolaryngology Head and Neck Surgery, Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsSpatial location of steatosis is closely related to the progression of metabolic dysfunction-associated steatohepatitis (MASH), and reports suggest lipid-associated macrophages (LAMs) facilitate this progression. However, the underlying mechanisms remain elusive. APPROACH AND

resultsSpatial transcriptomics (ST) data revealed a significant increase in myeloid cells and MASH-related genes in the hepatic periportal (PP) zone of MASH mice, suggesting a vital role of the PP zone in MASH progression. THRSP (SPOT14), involved in fatty acid synthesis, was markedly elevated in the livers of MASH patients and mice. Notably, CellPhoneDB analysis identified strong interactions between CD74 and macrophage migration inhibitory factor (MIF) within the Thrsp -high zone. Furthermore, Thrsp , Cd74 , Mif , Col3a1 , and LAMs markers were prominently colocalized in the hepatic PP zone of MASH mice, suggesting that Thrsp -mediated crosstalk in this region played a crucial role in MASH progression. Thrsp overexpression/knockout experiments confirmed that THRSP drove MASH progression by recruiting CD74 + LAMs mediated by MIF. Mechanistically, THRSP promoted hepatic palmitic acid (PA) synthesis, mainly by promoting hepatic de novo lipogenesis, and disturbing the binding of FASN-TRIM21, thereby inhibiting FASN ubiquitination. CD74 + LAMs were activated and recruited by chemokine-like MIF secreted from hepatocytes and macrophages stimulated with PA. Additionally, the compound C6, identified as a THRSP inhibitor, significantly ameliorated MASH in mice.

conclusionsOur study demonstrates that THRSP drives MASH progression by recruiting CD74 + LAMs mediated by MIF in the hepatic PP zone, providing novel insights into the spatial zonation and crosstalk between lipogenic hepatocytes and LAMs that may result in novel therapies for MASH.

Indexed as

Antigens, Differentiation, B-LymphocyteHepatocytesHistocompatibility Antigens Class IIIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMacrophagesNon-alcoholic Fatty Liver DiseaseAnimalsDisease Models, AnimalDisease ProgressionHumansLiverMaleMiceMice, Inbred C57BLMice, KnockoutAntigens, Differentiation, B-LymphocyteHistocompatibility Antigens Class IIIntramolecular Oxidoreductasesinvariant chainMacrophage Migration-Inhibitory FactorsMIF protein, humanMif protein, mousefatty acid synthaseinflammationliver microenvironmentpalmitic acidspatial zonation

Identifiers

PMID40590856
PMCPMC12991335

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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.