Journal
REDOX BIOLOGY
Volume 46, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.redox.2021.102131
Keywords
Fibroblast growth factor 21 (FGF21); Ferroptosis; Oxidative stress; Lipid peroxidation; Ubiquitination
Categories
Funding
- China National Key Research Projectof 13th Five Year Plan [2016YFD0501204]
- China Agricultural Research System [CARS-35]
- China Postdoctoral Science Foundation [2020T130455, 2019M653470]
- 111 project [D17015]
Ask authors/readers for more resources
Iron overload-induced ferroptosis in hepatocytes is promoted by excessive HO-1 expression, while FGF21 protein can protect against this process by inhibiting ferroptosis and preventing liver damage. These findings suggest that activating FGF21 could be an effective strategy for potential treatment of iron overload-induced ferroptosis-related diseases like hereditary haemochromatosis.
Ferroptosis plays a role in several diseases such as iron overload-induced liver diseases. Manipulation of ferroptosis has been explored as a potential therapeutic strategy to treat related diseases. Numerous antioxidants have been identified to control ferroptosis but the cell-autonomous mechanisms responsible for regulating ferroptosis remain elusive. In the present study, we found that iron overload promoted ferroptosis in hepatocytes by excessively inducing HO-1 expression, which contributed to the progression of liver injury and fibrosis, accompanied by the upregulation of the FGF21 protein level in vitro and in vivo. Interestingly, both recombinant FGF21 and Fgf21 overexpression significantly protected against iron overload-induced hepatocytes mitochondria damage, liver injury and fibrosis by inhibiting ferroptosis. In contrast, the loss of FGF21 aggravated iron overload-induced ferroptosis. Notably, FGF21-induced HO-1 inhibition (via the promotion of HO-1 ubiquitination and degradation) and NRF2 activation provide a mechanistic explanation for this phenomenon. Taken together, we identified FGF21 as a novel ferroptosis suppressor. Thus, FGF21 activation may provide an effective strategy for the potential treatment of iron overload-induced ferroptosis-related diseases, such as hereditary haemochromatosis (HH).
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available