Journal
FASEB JOURNAL
Volume 36, Issue 12, Pages -Publisher
WILEY
DOI: 10.1096/fj.202200933RR
Keywords
autophagy; curcumol; ferroptosis; hepatic fibrosis; NCOA4; therapeutic target
Categories
Funding
- The National Natural Science Foundation of China
- Guangxi Natural Science Foundation [82204755, 82160954, 81960751, 81960761, 81660705]
- Guangxi Young and Middle- aged Teachers' Research Ability Improvement Project [2020GXNSFBA297094]
- Guangxi University of Traditional Chinese Medicine School- level Project Youth Fund [GXZYZZ2020- 07, GXZYZZ2019- 1]
- Faculty of Chinese Medicine Science Guangxi University of Chinese Medicine Research Project [2020QN006]
- [2022MS008]
- [2022QJ001]
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In this study, it was found that curcumol promotes death of hepatic stellate cells and reduces extracellular matrix deposition. Additionally, curcumol triggers ferroptosis in activated hepatic stellate cells characterized by iron overload, lipid ROS accumulation, glutathione depletion, and lipid peroxidation. Moreover, curcumol promotes autophagy in hepatic stellate cells, which may be mediated by the degradation of NCOA4 and FTH1 complexes, leading to iron overload and induction of ferroptosis.
To explore the effect of curcumol on autophagy and ferroptosis of hepatic stellate cells, and to clarify the molecular mechanism of its anti-hepatic fibrosis. In the present study, we report that curcumol promotes the death of activated HSCs and reduces the deposition of extracellular matrix. Interestingly, curcumol treatment can trigger ferroptosis to eliminate activated HSCs characterized by iron overload, lipid ROS accumulation, glutathione depletion, and lipid peroxidation. Curcumol promotes HSC autophagy, which may be the key mechanism for its induction of ferroptosis. It is worth noting that the upregulation of nuclear receptor coactivator 4 (NCOA4) may play a key molecular mechanism. NCOA4 mediates the release of iron ions and induces the occurrence of ferroptosis. Overall, curcumol promotes autophagy in hepatic stellate cells, mediates the degradation of NCOA4 and FTH1 complexes, releases iron ions, leads to iron overload, and induces ferroptosis, which may be an important mechanism for its anti-hepatic fibrosis effect.
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