Ferroptosis-centered Disease Response Information
General Information of the Disease (ID: DIS00108)
Name |
Hepatoblastoma
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ICD |
ICD-11: DB91
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Full List of Target(s) of This Ferroptosis-centered Disease
Unspecific Target
In total 2 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Responsed Disease | Acute liver failure [ICD-11: DB91] | ||||
Responsed Drug | Glycyrrhizin | Phase 3 | |||
Responsed Regulator | High mobility group protein B1 (HMGB1) | Driver | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | L-02 cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_6926 | |
In Vivo Model |
In total, 40 male specific- pathogen-free C57BL/6 mice (Hubei Animal Experimental Center) 6-8 weeks old. The mice were randomly divided into 5 groups: The normal group, model group, 15 mg/kg GLY group, 30 mg/kg GLY group and 60 mg/kg GLY group. Except for the normal group, the other four groups of mice were injected intraperitoneally with D-GalN (400 mg/kg) and LPS (100 ug/kg) to induce the ALF model. According to a previous study on GLY gavage doses, three doses of GLY (15, 30 and 60 mg/kg/day) intervention groups were used. A total of 24 mice were divided into three groups. Mice received gavage with different doses of GLY for 3 days before induction of the ALF model.
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Response regulation | The HMGB1 inhibitor glycyrrhizin (GLY) significantly reduced the degree of ferroptosis during acute liver failure (ALF) by inhibiting oxidative stress. Treatment with GLY reduced the degree of liver damage, the expression of HMGB1 was decreased, and the levels of Nrf2, HO1 and GPX4 were increased. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [3] | ||||
Responsed Disease | Hepatoblastoma [ICD-11: DB91] | ||||
Responsed Regulator | BH3-interacting domain death agonist (BID) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Apoptosis | hsa04210 | ||||
Cell Process | Cell ferroptosis | ||||
Cell apoptosis | |||||
In Vitro Model | Hep-G2 cells | Hepatoblastoma | Homo sapiens | CVCL_0027 | |
Hep 3B2.1-7 cells | Hepatocellular carcinoma | Homo sapiens | CVCL_0326 | ||
MDA-MB-231 cells | Breast adenocarcinoma | Homo sapiens | CVCL_0062 | ||
HCT 116 cells | Colon carcinoma | Homo sapiens | CVCL_0291 | ||
Response regulation | Quercetin induced EB-mediated lysosome activation and increased ferritin degradation leading to ferroptosis and Bid-involved apoptosis in hepatoblastoma cells. | ||||
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Target for Ferroptosis | Marker/Suppressor | ||||
Responsed Disease | Acute liver failure [ICD-11: DB91] | ||||
Responsed Drug | Glycyrrhizin | Phase 3 | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | L-02 cells | Endocervical adenocarcinoma | Homo sapiens | CVCL_6926 | |
In Vivo Model |
In total, 40 male specific- pathogen-free C57BL/6 mice (Hubei Animal Experimental Center) 6-8 weeks old. The mice were randomly divided into 5 groups: The normal group, model group, 15 mg/kg GLY group, 30 mg/kg GLY group and 60 mg/kg GLY group. Except for the normal group, the other four groups of mice were injected intraperitoneally with D-GalN (400 mg/kg) and LPS (100 ug/kg) to induce the ALF model. According to a previous study on GLY gavage doses, three doses of GLY (15, 30 and 60 mg/kg/day) intervention groups were used. A total of 24 mice were divided into three groups. Mice received gavage with different doses of GLY for 3 days before induction of the ALF model.
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|
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Response regulation | The HMGB1 inhibitor glycyrrhizin (GLY) significantly reduced the degree of ferroptosis during acute liver failure (ALF) by inhibiting oxidative stress. Treatment with GLY reduced the degree of liver damage, the expression of HMGB1 was decreased, and the levels of Nrf2, HO1 and GPX4 were increased. | ||||
Cystine/glutamate transporter (SLC7A11)
In total 1 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [2] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Acute liver failure [ICD-11: DB91] | ||||
Responsed Regulator | Histone-lysine N-methyltransferase EZH2 (EZH2) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | hLCs (Liver cells) | ||||
mPHs (Mouse primary hepatocytes) | |||||
In Vivo Model |
Male C57BL/6 mice (n = 20, 6-8-week-old, b.w. 18-23 g) were purchased from SJA Laboratory Animal Co Ltd., Changsha, Hunan, China. Mice were given 600 mg/kg D-GalN (Sigma-Aldrich) and 30 ug/kg LPS (Sigma-Aldrich) by intraperitoneal injection. Mice in Sham group were received saline injection. For Fer-1 treatment, mice were received 10 mg/kg Fer-1 at 1 h prior to D-GalN and LPS injection. The wild-type (WT) or HBx-Tg mice were then subjected to D-GalN and LPS administration. For GSK126 treatment, wild-type (WT) or HBx-Tg mice were received GSK126 (150 mg/kg) prior to D-GalN and LPS administration.
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Response regulation | HBx facilitates ferroptosis in acute liver failure (ALF) via EZH2/H3K27me3-mediated SLC7A11 suppression. | ||||
References