Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10357)
Regulator Name Fibroblast growth factor 21 (FGF21)
Gene Name FGF21
Gene ID 26291
Regulator Type Protein coding
Uniprot ID Q9NSA1
Sequence
MDSDETGFEHSGLWVSVLAGLLLGACQAHPIPDSSPLLQFGGQVRQRYLYTDDAQQTEAH
LEIREDGTVGGAADQSPESLLQLKALKPGVIQILGVKTSRFLCQRPDGALYGSLHFDPEA
CSFRELLLEDGYNVYQSEAHGLPLHLPGNKSPHRDPAPRGPARFLPLPGLPPALPEPPGI
LAPQPPDVGSSDPLSMVGPSQGRSPSYAS

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Family Heparin-binding growth factors family
Function
Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity requires the presence of KLB. Regulates systemic glucose homeostasis and insulin sensitivity.

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HGNC ID
HGNC:3678
KEGG ID hsa:26291
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
FGF21 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Heme oxygenase 1 (HMOX1) [Driver; Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Driver/Suppressor
Responsed Disease Hereditary haemochromatosis ICD-11: 5C64
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 mPHs (Mouse primary hepatocytes)
In Vivo Model
In the adenovirus-mediated FGF21 over-expression mouse model, 12-week-old C57BL/6J male mice were divided into four groups: (1) EGFP vector overexpression + PBS injection group (n = 10), (2) EGFP vector overexpression + iron dextran injection group (n = 10), (3) FGF21-EGFP overexpression + PBS injection group (n = 10) and (4) FGF21-EGFP overexpression + iron dextran injection group (n = 10). The mice were administered PBS and iron dextran by intraperitoneal injection for 7 days.

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Response regulation FGF21 could protect hepatocytes from developing iron overload-induced ferroptosis by stimulating HO-1 ubiquitination and subsequent degradation. The FGF21HO-1 pathway could be targeted for treating iron overload-induced ferroptosis-related diseases, particularly hereditary haemochromatosis (HH).
Hereditary haemochromatosis [ICD-11: 5C64]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Fibroblast growth factor 21 (FGF21) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 mPHs (Mouse primary hepatocytes)
In Vivo Model
In the adenovirus-mediated FGF21 over-expression mouse model, 12-week-old C57BL/6J male mice were divided into four groups: (1) EGFP vector overexpression + PBS injection group (n = 10), (2) EGFP vector overexpression + iron dextran injection group (n = 10), (3) FGF21-EGFP overexpression + PBS injection group (n = 10) and (4) FGF21-EGFP overexpression + iron dextran injection group (n = 10). The mice were administered PBS and iron dextran by intraperitoneal injection for 7 days.

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Response regulation FGF21 could protect hepatocytes from developing iron overload-induced ferroptosis by stimulating HO-1 ubiquitination and subsequent degradation. The FGF21HO-1 pathway could be targeted for treating iron overload-induced ferroptosis-related diseases, particularly hereditary haemochromatosis (HH).
References
Ref 1 Fibroblast growth factor 21 attenuates iron overload-induced liver injury and fibrosis by inhibiting ferroptosis. Redox Biol. 2021 Oct;46:102131. doi: 10.1016/j.redox.2021.102131. Epub 2021 Sep 11.