%0 Journal Article
%A Blank, Valentin
%A Karlas, Thomas
%A Anderegg, Ulf
%A Wiegand, Johannes
%A Arnold, Josi
%A Bundalian, Linnaeus
%A Le Duc, Gabriela-Diana
%A Körner, Christiane
%A Ebert, Thomas
%A Saalbach, Anja
%+ Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society
%T Thy‐1 restricts steatosis and liver fibrosis in steatotic liver disease : 
%G eng
%U https://hdl.handle.net/21.11116/0000-000F-46EE-7
%R 10.1111/liv.15956
%7 2024-05-04
%D 2024
%* Review method: peer-reviewed
%X 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. © 2024 The Authors. Liver International published by John Wiley & Sons Ltd.
%K metabolic dysfunction-associated; metabolic dysfunction-associated steatohepatitis; steatotic liver disease; steatotic liver disease fibrosis; Thy-1
%J Liver International
%V 44
%N 8
%& 2075
%P 2075 - 2090
%@ 1478-32231478-3231