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Thy-1 restricts steatosis and liver fibrosis in steatotic liver disease.
Blank, Valentin; Karlas, Thomas; Anderegg, Ulf; Wiegand, Johannes; Arnold, Josi; Bundalian, Linnaeus; Le Duc, Gabriela-Diana; Körner, Christiane; Ebert, Thomas; Saalbach, Anja.
Afiliación
  • Blank V; Division of Gastroenterology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.
  • Karlas T; Division of Interdisciplinary Ultrasound, Department of Internal Medicine I - Gastroenterology and Pneumology, University Hospital Halle, Halle, Germany.
  • Anderegg U; Division of Gastroenterology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.
  • Wiegand J; Department of Dermatology, Venereology and Allergology, University of Leipzig Medical Center, Leipzig, Germany.
  • Arnold J; Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.
  • Bundalian L; Department of Dermatology, Venereology and Allergology, University of Leipzig Medical Center, Leipzig, Germany.
  • Le Duc GD; Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
  • Körner C; Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.
  • Ebert T; Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
  • Saalbach A; Division of Hepatology, Clinic of Oncology, Gastroenterology, Hepatology, and Pneumology, University Hospital Leipzig, Leipzig, Germany.
Liver Int ; 44(8): 2075-2090, 2024 Aug.
Article en En | MEDLINE | ID: mdl-38702958
ABSTRACT
BACKGROUND AND

AIMS:

Steatotic liver disease (SLD) is generally considered to represent a hepatic manifestation of metabolic syndrome and includes a disease spectrum comprising isolated steatosis, metabolic dysfunction-associated steatohepatitis, liver fibrosis and ultimately cirrhosis. A better understanding of the detailed underlying pathogenic mechanisms of this transition is crucial for the design of new and efficient therapeutic interventions. Thymocyte differentiation antigen (Thy-1, also known as CD90) expression on fibroblasts controls central functions relevant to fibrogenesis, including proliferation, apoptosis, cytokine responsiveness, and myofibroblast differentiation.

METHODS:

The impact of Thy-1 on the development of SLD and progression to fibrosis was investigated in high-fat diet (HFD)-induced SLD wild-type and Thy-1-deficient mice. In addition, the serum soluble Thy-1 (sThy-1) concentration was analysed in patients with metabolic dysfunction-associated SLD stratified according to steatosis, inflammation, or liver fibrosis using noninvasive markers.

RESULTS:

We demonstrated that Thy-1 attenuates the development of fatty liver and the expression of profibrogenic genes in the livers of HFD-induced SLD mice. Mechanistically, Thy-1 directly inhibits the profibrotic activation of nonparenchymal liver cells. In addition, Thy-1 prevents palmitic acid-mediated amplification of the inflammatory response of myeloid cells, which might indirectly contribute to the pronounced development of liver fibrosis in Thy-1-deficient mice. Serum analysis of patients with metabolically associated steatotic liver disease syndrome revealed that sThy-1 expression is correlated with liver fibrosis status, as assessed by liver stiffness, the Fib4 score, and the NAFLD fibrosis score.

CONCLUSION:

Our data strongly suggest that Thy-1 may function as a fibrosis-protective factor in mouse and human SLD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos Thy-1 / Dieta Alta en Grasa / Cirrosis Hepática / Ratones Endogámicos C57BL Límite: Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Liver Int Asunto de la revista: GASTROENTEROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos Thy-1 / Dieta Alta en Grasa / Cirrosis Hepática / Ratones Endogámicos C57BL Límite: Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Liver Int Asunto de la revista: GASTROENTEROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos