P53‐dependent induction of ferroptosis is required for artemether to alleviate carbon tetrachloride‐induced liver fibrosis and hepatic stellate cell activation

Wang, Ling; Zhang, Zili; Li, Mengmeng; Wang, Feixia; Jia, Yan; Zhang, Feng; Shao, Jiangjuan; Chen, Anping; Zheng, Shizhong

doi:10.1002/iub.1895

Cited by 135 publications

(100 citation statements)

References 48 publications

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“…Ferroptosis is a lipid-and iron-dependent form of cell death that is different from cell apoptosis, pyroptosis and autophagy. Recently, studies found that ferroptosis biomarkers (ROS, MDA and GPX4) have been detected in the tissues of fibrosis-related diseases [52][53][54]. In the present study, we found that the expression of ROS and MDA were upregulated in HFL1 cells treated with TGF-β1, but GPX4 expression was decreased.…”

Section: Agingsupporting

confidence: 61%

lncRNA ZFAS1 promotes lung fibroblast-to-myofibroblast transition and ferroptosis via functioning as a ceRNA through miR-150-5p/SLC38A1 axis

Yang

Tai

et al. 2020

Aging

140

108

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Pulmonary fibrosis (PF) is a lethal fibrotic lung disease. The role of lncRNAs in multiple diseases has been confirmed, but the role and mechanism of lncRNA zinc finger antisense 1 (ZFAS1) in the progression of PF need to be elucidated further. Here, we found that lncRNA ZFAS1 was upregulated in bleomycin (BLM)-induced PF rats lung tissues and transforming growth factor-β1 (TGF-β1)-treated HFL1 cells, and positively correlated with the expression of solute carrier family 38 member 1 (SLC38A1), which is an important regulator of lipid peroxidation. Moreover, knockdown of lncRNA ZFAS1 significantly alleviated TGF-β1-induced fibroblast activation, inflammation and lipid peroxidation. In vivo experiments showed that inhibition of lncRNA ZFAS1 abolished BLM-induced lipid peroxidation and PF development. Mechanistically, silencing of lncRNA ZFAS1 attenuated ferroptosis and PF progression by lncRNA ZFAS1 acting as a competing endogenous RNA (ceRNA) and sponging miR-150-5p to downregulate SLC38A1 expression. Collectively, our studies demonstrated the role of the lncRNA ZFAS1/miR-150-5p/SLC38A1 axis in the progression of PF, and may provide a new biomarker for the treatment of PF patients.

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Section: Agingsupporting

confidence: 61%

lncRNA ZFAS1 promotes lung fibroblast-to-myofibroblast transition and ferroptosis via functioning as a ceRNA through miR-150-5p/SLC38A1 axis

Yang

Tai

et al. 2020

Aging

140

108

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“…Therefore, effective suppression of inflammation and improvement of inflammatory microenvironment are critical to control the progression of liver fibrosis. Currently, anti‐inflammatory drugs have been widely used to control liver inflammation in clinical, of which, remarkable achievements has been made using natural products to prevention and treatment of liver fibrosis in experimental and clinical research . Tripterygium wilfordii Hook F (TwHF), a Chinese medicinal plant, shows potent anti‐inflammatory effect, especially in rheumatoid arthritis (RA).…”

Section: Discussionmentioning

confidence: 99%

Celastrol exerts anti‐inflammatory effect in liver fibrosis via activation of AMPK‐SIRT3 signalling

Wang

et al. 2019

J Cellular Molecular Medi

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Celastrol, a pentacyclic tritepene extracted from Tripterygium Wilfordi plant, showing potent liver protection effects on several liver‐related diseases. However, the anti‐inflammatory potential of celastrol in liver fibrosis and the detailed mechanisms remain uncovered. This study was to investigate the anti‐inflammatory effect of celastrol in liver fibrosis and to further reveal mechanisms of celastrol‐induced anti‐inflammatory effects with a focus on AMPK‐SIRT3 signalling. Celastrol showed potent ameliorative effects on liver fibrosis both in activated hepatic stellate cells (HSCs) and in fibrotic liver. Celastrol remarkably suppressed inflammation in vivo and inhibited the secretion of inflammatory factors in vitro. Interestingly, celastrol increased SIRT3 promoter activity and SIRT3 expression both in fibrotic liver and in activated HSCs. Furthermore, SIRT3 silencing evidently ameliorated the anti‐inflammatory potential of celastrol. Besides, we found that celastrol could increase the AMPK phosphorylation. Further investigation showed that SIRT3 siRNA decreased SIRT3 expression but had no obvious effect on phosphorylation of AMPK. In addition, inhibition of AMPK by employing compound C (an AMPK inhibitor) or AMPK1α siRNA significantly suppressed SIRT3 expression, suggesting that AMPK was an up‐stream protein of SIRT3 in liver fibrosis. We further found that depletion of AMPK significantly attenuated the inhibitory effect of celastrol on inflammation. Collectively, celastrol attenuated liver fibrosis mainly through inhibition of inflammation by activating AMPK‐SIRT3 signalling, which makes celastrol be a potential candidate compound in treating or protecting against liver fibrosis.

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“…Studies have shown that ferroptosis is closely related to the pathophysiological processes of more and more diseases. For example, ART treatment can significantly reduce the degree of liver injury and inhibit the formation of fibrotic scars in mice with liver fibrosis, in which the morphological characteristics of ferroptosis appear in hepatocytes 82 . Other studies have found that islets are indeed susceptible to ferroptosis in vitro.…”

Section: Ferroptosis and Other Diseasesmentioning

confidence: 99%

Ferroptosis: past, present and future

et al. 2020

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Ferroptosis is a new type of cell death that was discovered in recent years and is usually accompanied by a large amount of iron accumulation and lipid peroxidation during the cell death process; the occurrence of ferroptosis is iron-dependent. Ferroptosis-inducing factors can directly or indirectly affect glutathione peroxidase through different pathways, resulting in a decrease in antioxidant capacity and accumulation of lipid reactive oxygen species (ROS) in cells, ultimately leading to oxidative cell death. Recent studies have shown that ferroptosis is closely related to the pathophysiological processes of many diseases, such as tumors, nervous system diseases, ischemia-reperfusion injury, kidney injury, and blood diseases. How to intervene in the occurrence and development of related diseases by regulating cell ferroptosis has become a hotspot and focus of etiological research and treatment, but the functional changes and specific molecular mechanisms of ferroptosis still need to be further explored. This paper systematically summarizes the latest progress in ferroptosis research, with a focus on providing references for further understanding of its pathogenesis and for proposing new targets for the treatment of related diseases. Facts Ferroptosis is a new type of programmed cell death, which occurs with iron dependence. Ferroptosis plays an important regulatory role in the occurrence and development of many diseases, such as tumors, neurological diseases, acute kidney injury, ischemia/reperfusion, etc. Activating or blocking the ferroptosis pathway to alleviate the progression of the disease, which provides a promising therapeutic strategy for many diseases. Open questions What is the relationship between ferroptosis and other types of cell death? Is it synergy or antagonism? Is iron necessary to promote the production of lipid peroxides, or can other substances take the place of iron in ferroptosis? What is the downstream regulation mechanism of iron in ferroptosis? How can ferroptosis promote the development of inflammation?

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P53‐dependent induction of ferroptosis is required for artemether to alleviate carbon tetrachloride‐induced liver fibrosis and hepatic stellate cell activation

Cited by 135 publications

References 48 publications

lncRNA ZFAS1 promotes lung fibroblast-to-myofibroblast transition and ferroptosis via functioning as a ceRNA through miR-150-5p/SLC38A1 axis

lncRNA ZFAS1 promotes lung fibroblast-to-myofibroblast transition and ferroptosis via functioning as a ceRNA through miR-150-5p/SLC38A1 axis

Celastrol exerts anti‐inflammatory effect in liver fibrosis via activation of AMPK‐SIRT3 signalling

Ferroptosis: past, present and future

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