Macrophage‐Hepatocyte Circuits Mediated by Grancalcin Aggravate the Progression of Metabolic Dysfunction Associated Steatohepatitis
Abstract: The dynamic interplay between parenchymal hepatocytes and non‐parenchymal cells (NPCs), such as macrophages, is an important mechanism for liver metabolic homeostasis. Although numerous endeavors have been made to identify the mediators of metabolic dysfunction associated steatohepatitis (MASH), the molecular underpinnings of MASH progression remain poorly understood, and therapies to arrest MASH progression remain elusive. Herein, it is revealed that the expression of grancalcin (GCA) is upregulated in the macrophages of patients and rodents with MASH and correlates with MASH progression. Notably, the administration of recombinant GCA aggravates the development of MASH, whereas, Gca deletion in myeloid cells blunts liver steatosis and inflammation in multiple MASH murine models. Mechanistically, GCA activates macrophages via TLR9‐NF‐κB signaling, and the activated macrophages promote hepatocyte lipid accumulation and apoptosis via secretion of Interleukin‐6 (IL‐6), Tumor Necrosis Factor α (TNFα), and Interleukin‐1β(IL‐1β), thereby leading to hepatic steatosis and inflammation. Finally, the therapeutic administration of antibody blocking GCA effectively halts the progression of MASH. Collectively, these findings implicate GCA as a crucial mediator of MASH and clarify a new metabolic signaling axis between the hepatocytes and macrophages, implying that GCA can emerge as a particularly interesting putative therapeutic target for reversing MASH progression.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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Macrophage‐Hepatocyte Circuits Mediated by Grancalcin Aggravate the Progression of Metabolic Dysfunction Associated Steatohepatitis ; day:16 ; month:09 ; year:2024 ; extent:19
Advanced science ; (16.09.2024) (gesamt 19)
- Urheber
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Su, Tian
He, Yue
Wang, Min
Zhou, Haiyan
Huang, Yan
Ye, Mingsheng
Guo, Qi
Xiao, Ye
Cai, Guangping
Zhao, Mingyang
Wang, Jianping
Luo, Xianghang
- DOI
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10.1002/advs.202406500
- URN
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urn:nbn:de:101:1-2409161408464.318319960497
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:36 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Su, Tian
- He, Yue
- Wang, Min
- Zhou, Haiyan
- Huang, Yan
- Ye, Mingsheng
- Guo, Qi
- Xiao, Ye
- Cai, Guangping
- Zhao, Mingyang
- Wang, Jianping
- Luo, Xianghang
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