Ferroptosis and Liver Fibrosis

Pan, Qi; Luo, Yi; Xia, Qiang; He, Kang

doi:10.7150/ijms.62903

Cited by 76 publications

(50 citation statements)

References 58 publications

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“…The study of treatment at the liver fibrosis stage is important and urgent. Researchers continue to explore therapeutic measures for liver fibrosis, including extracting compounds from natural plants to develop new drugs [ 16 ], and identifying the causes and therapeutic targets of liver fibrosis [ 8 , 17 , 18 , 19 , 20 ]. In this study, a single compound, phloridzin, was extracted from lychee seed to determine its mechanism of action in the treatment of liver fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Phloridzin Reveals New Treatment Strategies for Liver Fibrosis

et al. 2022

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Liver fibrosis is an urgent public health problem which is difficult to resolve. However, various drugs for the treatment of liver fibrosis in clinical practice have their own problems during use. In this study, we used phloridzin to treat hepatic fibrosis in the CCl4-induced C57/BL6N mouse model, which was extracted from lychee core, a traditional Chinese medicine. The therapeutic effect was evaluated by biochemical index detections and ultrasound detection. Furthermore, in order to determine the mechanism of phloridzin in the treatment of liver fibrosis, we performed high-throughput sequencing of mRNA and lncRNA in different groups of liver tissues. The results showed that compared with the model group, the phloridzin-treated groups revealed a significant decrease in collagen deposition and decreased levels of serum alanine aminotransferase, aspartate aminotransferase, laminin, and hyaluronic acid. GO and KEGG pathway enrichment analysis of the differential mRNAs was performed and revealed that phloridzin mainly affects cell ferroptosis. Gene co-expression analysis showed that the target genes of lncRNA were obvious in cell components such as focal adhesions, intercellular adhesion, and cell–substrate junctions and in metabolic pathways such as carbon metabolism. These results showed that phloridizin can effectively treat liver fibrosis, and the mechanism may involve ferroptosis, carbon metabolism, and related changes in biomechanics.

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Section: Discussionmentioning

confidence: 99%

Phloridzin Reveals New Treatment Strategies for Liver Fibrosis

et al. 2022

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“…For instance, the use of both iron chelator and antioxidants have been proposed as therapeutic tools in the treatment of myocardial infarction and in preconditioning the hearts of patients undergoing reperfusion manoeuvres [ 135 ]. In liver, several physiopathological pathways can be affected by impaired iron homeostasis including alcohol-induced hepatotoxicity [ 136 ], acute liver failure [ 85 ], drug-induced liver injury [ 137 ], and hepatic fibrosis [ 138 ]. Thus, clarifying the subtle mechanisms that regulate iron balance within hepatocytes is of paramount importance in the attempt to mitigate the clinical outcome of the above-mentioned pathologies.…”

Section: Discussionmentioning

confidence: 99%

Iron Overload, Oxidative Stress, and Ferroptosis in the Failing Heart and Liver

et al. 2021

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Iron accumulation is a key mediator of several cytotoxic mechanisms leading to the impairment of redox homeostasis and cellular death. Iron overload is often associated with haematological diseases which require regular blood transfusion/phlebotomy, and it represents a common complication in thalassaemic patients. Major damages predominantly occur in the liver and the heart, leading to a specific form of cell death recently named ferroptosis. Different from apoptosis, necrosis, and autophagy, ferroptosis is strictly dependent on iron and reactive oxygen species, with a dysregulation of mitochondrial structure/function. Susceptibility to ferroptosis is dependent on intracellular antioxidant capacity and varies according to the different cell types. Chemotherapy-induced cardiotoxicity has been proven to be mediated predominantly by iron accumulation and ferroptosis, whereas there is evidence about the role of ferritin in protecting cardiomyocytes from ferroptosis and consequent heart failure. Another paradigmatic organ for transfusion-associated complication due to iron overload is the liver, in which the role of ferroptosis is yet to be elucidated. Some studies report a role of ferroptosis in the initiation of hepatic inflammation processes while others provide evidence about an involvement in several pathologies including immune-related hepatitis and acute liver failure. In this manuscript, we aim to review the literature to address putative common features between the response to ferroptosis in the heart and liver. A better comprehension of (dys)similarities is pivotal for the development of future therapeutic strategies that can be designed to specifically target this type of cell death in an attempt to minimize iron-overload effects in specific organs.

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“…These mechanisms include cytokine and growth factor release [ 153 , 154 ], EMT transition [ 117 ], collagen regulation [ 155 , 156 ], or the immune regulation of HCC hepatocytes [ 157 ], among others. That is the case for TTP with several important effects in the different stages of fibrosis [ 119 , 126 , 135 , 158 ]. For instance, TTP has been shown to regulate the mRNA of several cytokines and chemokines (including IL-17, TNFα, IL-6, IL-1β, and CXCL1-2) and in several cell lines (macrophages, lymphocytes, endothelial cells, and MFB) [ 126 , 140 , 153 ].…”

Section: Discussionmentioning

confidence: 99%

“…Another mechanism by which HuR was reported to regulate HSCs effects in fibrogenesis is through the alleviation of HSCs by promoting their death by ferroptosis [ 134 ]. This type of cell death occurs due to the excessive accumulation of ROS and β-oxidation-dependent redox imbalance [ 135 ]. In this regard, the upregulation of HuR resulted in the stabilization of the mRNA of beclin1, promoted autophagic-dependent ferritin degradation, and eventually led to the induction of ferroptosis [ 136 ].…”

Section: Rbps Regulation Of Hsc Metabolic Reprogrammingmentioning

confidence: 99%

Metabolic Reprogramming of Liver Fibrosis

Delgado

Cárdenas

Farran

et al. 2021

Cells

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Liver fibrosis is an excessive and imbalanced deposition of fibrous extracellular matrix (ECM) that is associated with the hepatic wound-healing response. It is also the common mechanism that contributes to the impairment of the liver function that is observed in many chronic liver diseases (CLD). Despite the efforts, no effective therapy against fibrosis exists yet. Worryingly, due to the growing obesity pandemic, fibrosis incidence is on the rise. Here, we aim to summarize the main components and mechanisms involved in the progression of liver fibrosis, with special focus on the metabolic regulation of key effectors of fibrogenesis, hepatic stellate cells (HSCs), and their role in the disease progression. Hepatic cells that undergo metabolic reprogramming require a tightly controlled, fine-tuned cellular response, allowing them to meet their energetic demands without affecting cellular integrity. Here, we aim to discuss the role of ribonucleic acid (RNA)-binding proteins (RBPs), whose dynamic nature being context- and stimuli-dependent make them very suitable for the fibrotic situation. Thus, we will not only summarize the up-to-date literature on the metabolic regulation of HSCs in liver fibrosis, but also on the RBP-dependent post-transcriptional regulation of this metabolic switch that results in such important consequences for the progression of fibrosis and CLD.

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Ferroptosis and Liver Fibrosis

Cited by 76 publications

References 58 publications

Phloridzin Reveals New Treatment Strategies for Liver Fibrosis

Phloridzin Reveals New Treatment Strategies for Liver Fibrosis

Iron Overload, Oxidative Stress, and Ferroptosis in the Failing Heart and Liver

Metabolic Reprogramming of Liver Fibrosis

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