Specific knockdown of Y-box binding protein 1 in hepatic progenitor cells inhibits proliferation and alleviates liver fibrosis.

Autor: Li B; Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China., Li F; Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China., Gu T; Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China., Guo Y; Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China., Shen B; Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China., Xu X; Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China., Shen Z; Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China., Chen L; Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China., Zhang Q; Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China., Dong H; Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China., Cai X; Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China. Electronic address: caixiaobo19790719@126.com., Lu L; Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201620, China. Electronic address: lungenlu1965@163.com.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2022 Apr 15; Vol. 921, pp. 174866. Date of Electronic Publication: 2022 Feb 26.
DOI: 10.1016/j.ejphar.2022.174866
Abstrakt: The proliferation of hepatic progenitor cells (HPCs) contributes to liver regeneration and fibrogenesis during chronic liver injury; however, the mechanism modulating HPC proliferation remains unknown. Y-box binding protein-1 (YB-1) is a transcription factor that regulates the transcription of several genes and is highly expressed in liver injury. We explored the role of YB-1 in HPC proliferation and liver fibrosis. We detected increased expansion of HPCs and elevated levels of YB-1 in HPCs from patients with hepatitis B virus-related fibrosis and choline-deficient ethionine-supplemented or 5-diethoxycarbonyl-1,4-dihydrocollidine diet-induced mice compared with those in control groups. HPC-specific deletion of YB-1 using YB-1 flox/flox ; Foxl1-Cre +/- mice led to reduced HPC expansion and less collagen deposition in the liver tissues compared with that in Cre -/- mice. In cultured primary HPCs, YB-1 knockdown inhibited HPC proliferation. Further experiments indicated YB-1 negatively regulated p53 expression, and silencing of p53 blocked YB-1 knockdown-mediated inhibition of HPC proliferation. Collectively, YB-1 negatively regulates HPC proliferation and alleviates liver fibrosis by p53.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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