ReferenceID 5683
Matrine promotes hepatic oval cells differentiation into hepatocytes and alleviates liver injury by suppression of Notch signalling pathway
Life Sci
AIMS: Recent studies have shown that the hyperactive Notch pathway is involved in cirrhosis and hepatocellular carcinoma (HCC) development by regulating differentiation of hepatic oval cells (HOCs) into cancer cells. The
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Record Fields
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- Reference Id
- 5683
- Evidence Id
- 22273
- Core Evidence Id
- 22273
- Source Reference Id
- 4611
- Herb2 Reference Id
- HBREF005408
- Subject Paper Key
- HBIN034558_32866517
- Pubmed Id
- 32866517
- Doi
- 10.1016/j.lfs.2020.118354
- Paper Title
- Matrine promotes hepatic oval cells differentiation into hepatocytes and alleviates liver injury by suppression of Notch signalling pathway
- Paper Abstract
- AIMS: Recent studies have shown that the hyperactive Notch pathway is involved in cirrhosis and hepatocellular carcinoma (HCC) development by regulating differentiation of hepatic oval cells (HOCs) into cancer cells. The aim of this study was to investigate whether matrine can alleviate liver injury and promote HOC differentiation into hepatocytes by suppression of Notch pathway. MAIN METHODS: We evaluated the expression of Notch-1, Jagged-1, and Hes-1 in HCC tissue by immunohistochemistry. Stem cell characteristics of HOCs were evaluated by CCK-8, cell cycle, and apoptosis. The expression of Notch pathway, HOC markers and albumin (ALB) was detected by immunohistochemistry, QRT-PCR and western blotting. The effects of matrine in protecting liver in vivo were investigated in a rat Solt-Farber precancerous model. KEY FINDINGS: We found an abnormal activated Notch pathway in HCC tissue, and the hyperactive Notch pathway was strongly associated with poor liver function in patients with cirrhosis with HCC. Using siNotch-1 to inhibit Notch pathway confirmed that Notch pathway could maintain stem cell characteristics of HOCs. Matrine inhibited stem cell characteristics of HOCs, the expression of Notch pathway and HOC markers but upregulated ALB. Matrine in combined with siNotch-1 RNA decreased the more potently inhibited HOC markers and Notch pathway. In rat Solt-Farber precancerous model, prophylactic application of matrine alleviated liver injury, downregulated Notch pathway and HOC markers, and upregulated ALB in a dose-dependent manner. SIGNIFICANCE: Matrine could promote the differentiation of HOCs into hepatocytes by inhibiting the Notch signalling pathway and alleviate liver injury.
- Journal
- Life Sci
- Publish Year
- 2020
- Experiment Subject
- rat; patient
- Experiment Type
- Cell Experiment
- Phenotype Related
- Cirrhosis; Solt-farber Precancerous; Cancer; Hepatocellular Carcinoma; Liver Injury
- Paper Title Cn
- Paper Title En
- Matrine promotes hepatic oval cells differentiation into hepatocytes and alleviates liver injury by suppression of Notch signalling pathway
- Bilingual Status
- semi_complete