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Cited by 16Liver Disease Diagnosis and TreatmentLiver physiology and pathologyMacrophage Migration Inhibitory Factor

The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.

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

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Xu, Xu, Li, Huagen, Lin, Hai, Li, Qichao, Liu, Yuenan, Huang, Weijun, Yang, Jundong, Li, Niannian, Gao, Zhenfei, Wang, Shengming, Shen, Hangdong, Xue, Wenjun, Yuan, Haolin, Wang, Wei, Shuai, Jianwei, Liu, Junli, Yin, Shankai, Liu, Feng·2026·Hepatology
DOI 10.1097/hep.0000000000001429PMC PMC12991335
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Abstract

Background and Aims: Spatial 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 Results: Spatial 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. Conclusions: Our 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.

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  • Hepatocyte-derived THRSP promotes palmitic acid and MIF secretion to recruit CD74+ LAMs, creating a localized pro-inflammatory and pro-fibrogenic niche.

    “Here, hepatocyte-derived thyroid hormone-responsive protein (THRSP) promotes palmitic acid (PA) and macrophage migration inhibitory factor (MIF) secretion to recruit CD74+ LAMs, creating a localized pro-inflammatory and pro-fibrogenic niche (58).”

    From Macrophage duality in liver diseases: heterogeneity, plasticity, and the quest for precision therapeutics (2026) · cites this paper as [58]

    The Discussion (page unavailable) says THRSP drives hepatic palmitic acid (PA) accumulation and that hepatocyte-derived PA stimulates MIF secretion, recruiting CD74+ LAMs to the periportal zone. The Results also link THRSP overexpression to periportal inflammation and fibrosis. The copy supports PA production and accumulation, but does not establish the claim’s more specific assertion that THRSP promotes PA secretion. (LLM, conf=0.84)

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Research works printed but not linked: 40

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Metadata

Authors
Xu, X., Li, H., Lin, H., Li, Q., Liu, Y., Huang, W., Yang, J., Li, N., Gao, Z., Wang, S., Shen, H., Xue, W., Yuan, H., Wang, W., Shuai, J., Liu, J., Yin, S., & Liu, F.
Affiliations
  • Shanghai Jiao Tong University (CN)
  • Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
  • Wenzhou Institute, University of Chinese Academy of Sciences (CN)
  • Wenzhou Medical University (CN)
  • Department 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
  • Zhejiang Lab (CN)
Corresponding author
  • Li, Qichao
  • Liu, Yuenan
  • Shuai, Jianwei
  • Liu, Junli
  • Yin, Shankai
  • Liu, Feng
ORCID
Venue
Hepatology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2025-06-12
Volume
83
Issue
4
Pages
868-887
ISSN
  • 0270-9139 (ISSN-L)
  • 1527-3350
DOI
10.1097/hep.0000000000001429
PMC
PMC12991335
OpenAlex
W4411873897
Cited by
16
References
13
Citations by year
2026: 14 · 2025: 2
FWCI
11.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Hepatology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China
  • China Postdoctoral Science Foundation
  • Shanghai Jiao Tong University
Topics
  • Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Immunology and Microbiology › Immunology › Macrophage Migration Inhibitory Factor
Keywords
nonalcoholic steatohepatitis, THRSP, CD74, macrophage migration inhibitory factor, lipid-associated macrophages, de novo lipogenesis, palmitic acid, TRIM21, fatty acid synthesis, spatial transcriptomics, hepatic steatosis
MeSH terms
Animals, Antigens, Differentiation, B-Lymphocyte, Histocompatibility Antigens Class II, Disease Models, Animal, Humans, Liver, Macrophage Migration-Inhibitory Factors, Macrophages, Male, Mice, Inbred C57BL, Mice, Knockout, Disease Progression, Intramolecular Oxidoreductases, Hepatocytes, Mice, Non-alcoholic Fatty Liver Disease

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