Three-dimensional analysis of ductular reactions and their correlation with liver regeneration and fibrosis.

Autor: Yoshizawa T; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki Aomori, Japan., Lee JW; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Hong SM; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea., Jung D; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Medicine, Graduate School, University of Ulsan, Seoul, Republic of Korea., Noë M; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Zbijewski W; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA., Kiemen A; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA., Wu PH; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA., Wirtz D; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA., Hruban RH; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Wood LD; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Oshima K; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. koshima3@jhmi.edu.
Jazyk: angličtina
Zdroj: Virchows Archiv : an international journal of pathology [Virchows Arch] 2024 May; Vol. 484 (5), pp. 753-763. Date of Electronic Publication: 2023 Sep 14.
DOI: 10.1007/s00428-023-03641-3
Abstrakt: The liver has multiple regeneration modes, including hepatocellular hypertrophy and self-renewal of hepatocytes. When hepatocyte proliferation is impaired, hepatic progenitor cells may proliferate through ductular reaction (DR), differentiate into hepatocytes, and contribute to fibrosis. However, the three-dimensional spatial relationship between DR and regenerating hepatocytes and dynamic changes in DR associated with fibrosis remain poorly understood. Here, we performed three-dimensional (3D) imaging of cleared 42 liver explants with chronic and acute liver diseases and 4 normal livers to visualize DR. In chronic hepatic liver diseases, such as viral hepatitis, steatohepatitis, autoimmune hepatitis, and cryptogenic cirrhosis, the total length and number of branches of DR showed a significant positive correlation. We studied the spatial relationship between DR and GS-expressing cells using glutamine synthetase (GS) and cytokeratin 19 (CK19) as markers of liver regeneration and DR, respectively. The percentage of CK19-positive cells that co-expressed GS was less than 10% in chronic liver diseases. In contrast, nearly one-third of CK19-positive cells co-expressed GS in acute liver diseases, and chronic cholestatic liver diseases, including primary biliary cholangitis and primary sclerosing cholangitis, showed no co-expression. We also found that DR was longer and had more branching in livers with progressive fibrosis compared to those with regressive fibrosis. Our results suggest that DR displays varying degrees of spatial complexity and contribution to liver regeneration. DR may serve as hepatobiliary junctions that maintain continuity between hepatocytes and bile ducts rather than hepatocyte regeneration in chronic liver diseases.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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